Formulation and Evaluation of Ethenzamide pharmacosomal gel

ABSTRACT

The present study was focused on developing and evaluating Ethenzamide containing
Pharmacosomal gel formulation for In vitro studies. Pharmacosomal formulations were
prepared by using Solvent evaporation method and were evaluated for In vitro
characteristics, stability studies. Pharmacosomal formulation displayed highest entrapment
efficiency with desired particle size. SEM analyses showed that Pharmacosomal formulation
was spherical in shape. Pharmacosomes containing lipid higher percentage of drug release
after 8 hours as compared to other formulations. F3 formulation was found to be stable at
the end of the study on storage condition. The present study suggested that Pharmacosomal
gel formulations provide sustained and prolonged delivery of drug with enhance
bioavailability.

Keywords: Pharmacosomal gel, Ethenzamide, Solvent evaporation method, in vitro drug

release.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

1. INTRODUCTION

Vesicles are the structures that are small in size having a bilayer arrangement similar to the
natural lipid bilayer structure of our body membrane. They are highly efficient in encapsulating drugs
having varied physico-chemical properties. Stratum corneum is regarded as the major hindrance in
attaining a good penetration of drugs applied transdermally and is easily overcome by these
vesicular structures. Amphiphilic nature of vesicles helps to deliver both hydrophilic as well as
lipophilic drugs to their respective targets with relative ease. Liposomes were developed earlier as
pioneer model in vesicular delivery system. Vesicles contribute greatly in cellular communication as
well as particle transport. Researchers have revealed their conclusion that the vesicular morphology
helps them to deliver drugs in efficient manner and vesicles can be tagged for cell specificity, thus
producing a targeted action. The liposomes were further modified for better features which lead
to the discovery of pharmacosomes which is considered by many as one of the major advancement
and advantage in vesicular research. Vesicular systems are as follows:
Liposomes
They are microscopic sized water containing vesicles similar in structure to skin phospholipid bilayer
structure. The phospholipid chain from soya or egg yolk and cholesterol in some cases. Mezei was the
pioneer in using liposomes as carrier agents for delivery. It only helped the drug to reach the reservoir
in the upper layer of skin and no percutaneous absorption was achieved thus addressing the need of
newer methods. Certain studies showed enhanced deposition of miconazole nitrate in upper skin
strata with minimum penetrability when liposomes were used.
Niosomes
They are similar to classical liposomes in their composition except for the use of non ionic surfactants
thus giving them higher stability and lesser cost. The mechanisms depends on physico-chemical
properties of drug, vesicle type as well as lipids used. Fluconazole niosomes with span 60, span
40 and brij 72 prepared by thin film hydration method exhibited sustained drug release and higher
cutaneous retention. Cyclopirox is another drug delivered with better efficiency in a different study.

Transferosomes
They are also known as ultra deformable vesicles or liposomes due to greater elasticity and
deformability. Phospholipids along with surfactants of different types provide the flexibility and
is used as an efficient delivery system for transdermal as well as topical delivery of drugs, genetic
materials and vaccines study of clotrimazole loaded ethosomes lead to the finding that the drug
flux was found to be more in the system than normal transferosomes which ultimately proved the
higher efficiency of ethosomes as a vesicular delivery system.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Spingosomes
They are concentric bilayered vesicles where the aqueous compartment is completely enclosed
by bilayered membrane composed of natural or synthetic spingolipids and has a size range of
0.05 to 0.45 microns. They are more stable and have increased circulation time compared to
normal vesicular systems because they are made of only amide and ether linkages with lesser number
of double bonds than lecithin.
Virosomes
Virosomes are spherical, unilamellar phospholipid bilayered vesicles incorporating virus derived
proteins so that it can fuse with target cells. The nucleocapsid and genetic material of source virus
is incorporated within the envelope and for influenza virus resistance, lipids are intercalated with
membrane proteins like haemagglutinin and neuraminidase thus enabling them to transfer the
drug to target cell cytoplasm. The viral surface glycoprotein is contained in the vesicles and size ranges
from 120-180 nanometers.
Aquasomes
It is a three layered self assembled nanoparticle system with ceramic carbon nanocrystalline particulate
core coated with glassy cellobiose that helps in specific targeting and molecular shielding. They are
designed to deliver proteins, peptides, vaccines, and genes while preserving their biological activity.
Aquasomes mimic natural biological systems, offering high stability, biocompatibility, and controlled
drug release, making them ideal for sensitive therapeutic agents.
Cubosomes
Cubosomes are nano-structured liquid crystalline particles used as advanced drug delivery
systems. They are formed from lipid molecules that self-assemble in water to create a
bicontinuous cubic phase, which has a unique 3D honeycomb-like structure. These are systems which
have been experimentally put into use for herbal medicine delivery for the KIOM-MA 128 drug used
in atopic dermatitis treatment. The permeation feature of M-A 128 was enhanced using cubosomes
compared to suspension form.

PHARMACOSOMES

Some of the limitation which have been encountered in transferosomes are because of their
predisposition to oxidative degradation & purity of natural phospholipids, which overcome by
pharmacosomes. The prodrug conjoins hydrophilic and liphophilic properties, and therefore acquires
amphiphilic characters. Similar to other vesicle forming components, it was found to reduce
interfacial tension and at higher concentrations exhibits mesomorphic behavior. The term
pharmacosomes is explicitly used to describe the zwitterionic, amphiphilic, stoichiometric complexes
of polyphenolic compounds with phospholipids. These are the lipid based drug delivery systems
that are appropriately elaborated as the colloidal dispersions of drugs having a covalent, being
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amphiphilic compounds facilitate membrane, tissue, or cell wall transfer in the organism. They are
an effective tool to achieve desired therapeutic goals such as drug targeting and controlled release.
The criterion for the development of the vesicular pharmacosomes is dependent on surface and bulk
interactions of lipids with drug. Any drug possessing an active hydrogen atom (-COOH, -OH, -NH2,
etc) can be esterified to the lipid, with or without spacer chain that strongly result in an amphiphilic
compound.
The Salient Features of Pharmacosomes
• Encaptured volume and drug-bilayer interactions do not influence entrapment efficiency, in case
of Pharmacosomes.
• Due to their amphiphilic nature, such systems enable multiple pathways of transport after drug
administration, including passage through lipophilic membranes or tissues, cellular uptake via
piggyback endocytosis, and release through exocytosis.
• Unlike liposome, there is no need of following the tedious, time-consuming step for removing the
free, unentrapped drug from the formulation.

• The drug is released from pharmacosomes by hydrolysis (including enzymatic).

• Phospholipids transfer/exchange is reduced, and solubilization by HDL is low.
• No problem occurs in drug incorporation.
• The physicochemical stability of the pharmacosomes depends upon the physicochemical properties
of the drug- lipid complex.
• Entrapment efficiency is not only high but predetermined, because drug itself in conjugation with
lipids forms vesicles.
• Following absorption, their degradation velocity into active drug molecule depends to a great
extent on the size and functional groups of drug molecule, the chain length of the lipids, and the spacer.
These can be varied relatively precisely for optimized in vivo pharmacokinetic.

Limitation of Pharmacososmes
• The leakage of drug can be protected by the formation of covalent bond.
• For the synthesis of compound, the amphiphilic nature is required.

• The basic principle for pharmacosomes is surface and bulk interaction of lipid with drug

• The pharmacosomes undergo fusion, aggregation as well as hydrolysis when they set on storage.

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Advantages
• These are suitable for both hydrophilic and lipophilic drugs.
• The aqueous solution of these amphiphilic exhibit’s concentration dependent aggregation
• High and predetermined entrapment efficiency as drug and carrier form a stoichiometrically
defined unit covalently linked together.
• Volume of inclusion doesn’t influence entrapment efficiency.
• No need of removing the free, unentrapped drug from the formulation which is required in the
case of liposome.
• As drug is covalently bound, membrane fluidity has no effect on release rate, but in turn depends
upon the phase-transition temperature of the drug-lipid complex.
• No leakage of drug take place as the drug is covalently linked to the carrier.
• Drug can be delivered directly to the site of infection.
• Their degradation velocity into active drug molecule, after absorption depends very much on the
size and functional groups of the drug molecule, the chain length of the lipids, and the spacer.
• Improves bioavailability especially in the case of poorly soluble drugs.
• Reduction in adverse effects and toxicity.

Disadvantages
• Synthesis of a compound depends upon its amphiphilic nature.
• Required surface and bulk interaction of lipids with drugs.
• Required covalent bonding to protect the leakage of drugs.
• On storage, undergo fusion and aggregation, as well as chemical hydrolysis.

Components of Pharmacosomes
For a delivery system, three components are Drugs, solvent and carries (lipid).

Drugs
Any drug possessing an active hydrogen atom (-COOH, -OH,-NH2 etc) can be esterified to the
lipid, with or without spacer chain resulting into amphiphilic complexes. These synthesized
amphiphilic complexes (pharmacosome), facilitate membrane, tissue, or cell wall transfer, in the
organism.

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Solvent
An analytical grade organic solvent is required for the preparation of pharmacosome. It must be
of high purity and volatile in nature. The PLs and the drug must be dissolved in the selected
solvent either simply by its addition or by refluxing. The selection of solvent depends on polarity
of the drug and the lipid. A solvent with intermediate polarity is selected for pharmacosome
preparation.
Lipids

Lipid or lecithin is the principal molecular building block of cell membranes. It is miscible both
in water and in oil / lipid environment and well absorbed orally. Lecithin is a dietary supplement
in two forms: as granular lecithin and a capsule, containing dispersion in oil.
Method of Preparations
In general two methods have been employed to prepare pharmacosomes.
• Hand-shaking method.
• Ether-injection method.

Hand-shaking method or solvent evaporation

In hand-shaking method, the dried film of drug lipid complex deposited in a round bottom flask upon
hydration with aqueous medium readily gives vesicular suspension. In the drug lipid complex
usually, lecithin is added many a times to reduce surface tension of the complex, so when
reconstituted in an aqueous medium gives good surface wetting properties.
Water is usually used as an aqueous phase.

Ether injection method

In ether injection method, organic solution of drug lipid complex was injected slowly into the aqueous
medium, wherein the vesicles were readily formed. Here the drug lipid complex is mixed with ether
which acts as a solvent and then it is slowly injected in the aqueous medium and spontaneous
formation of vesicles takes place.

GELS

Gels are defined as semi rigid systems in which the movement of the dispersing medium is restricted
by an interlacing three-dimensional network of particles or solvated super molecules of the dispersed
phase. The USP defines gels (sometimes called jellies) as semisolid systems containing either
suspensions made up of small inorganic particles, or large organic molecules diffused by a liquid,
where the gel mass contains a network of small separate particles, The gel is classified as a two-phase
system. In this, if the particle size of the dispersed phase is relatively large, the gel mass is sometimes

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

called as a magma. Single phase gels consist of organic super molecules uniformly distributed
throughout a liquid in such a way that no apparent boundaries occur between the dispersed super
molecules and the liquid.

Properties of Gels.
1. The gelling agent must be inert, safe and cannot react with other constituents.
2. The gelling agent should produce a functional solid-like nature at the time of storage which is easily
broken when exposed to shear forces produced by squeezing the tube, trembling the bottle or at the
time of topical application.
3. It should have appropriate anti-microbial agent.
4. The topical gel must not be gluey.
5. The ophthalmic gel must be sterilized.
6. The apparent viscosity or gel strength increases with an increase in the effective crosslink density of
the gel.
7. They exhibit the mechanical features of the solid state.
8. Each constituent is continuous throughout the system.
9. There is high degree of attraction amongst the dispersed phase and water medium so the gels
remain equally distributed upon standing and doesn’t freely settle.

Uses of Gels
1. As delivery systems for orally administered drugs.
2. For topical drugs applied directly to the skin, mucous membrane or the eye.
3. As long-acting forms of drug injected intramuscularly or implanted into the body.
4. As binders in tablet granulation, protective colloids in suspensions, thickeners in oral liquid and
suppository bases.
5. In cosmetics like shampoos, fragrance products, dentifrices and skin and hair care preparations.
6. Lubricant for catheters.
7. Bases for patch testing.

8. Sodium chloride gel for electrocardiography.

9. Sodium fluoride & Phosphoric acid gel for dental care prophylactic

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EVALUATION PARAMETERS
Scanning electron microscopy (SEM)
SEM was used to determine the size of the particle and its appearance. Dry sample was placed on
electron microscope brass stub coated with gold in an ion sputter. Random scanning of the
complex at 100.

Drug entrapment and loading capacity

Drug pharmacosomal complex was centrifuged at 10000 rpm for 90 minutes at 4°C to separate
pharmacosomal from the untrapped drug. The concentration of free drug can be measured by
doing ultraviolet spectroscopy. The percentage drug entrapment can be calculated as given
formula:
Weight of total drug – Entrapment efficiency % = weight of free drug weight of total drug×100
Fourier transform infrared spectroscopy (FTIR) analysis
FTIR analysis done for checking the structure as well as chemical stability of drug, phospholipid. The
Pharmacosomal drug will be crushed with potassium bromide to obtain pellets at 600 kg/cm² pressure.
Scanning will be done between the ranges of 4000-400 cm ¹.
Size analysis and zeta potential
Malvern Zetasizer is used to check the particle size and zeta size of Pharmacosomal complex.
Argon laser is used for this particle size and zeta sizer characterization.

Applications
• Pharmacosomes show wider stability profile and longer shelf life.
• Pharmacosomes have the capacity to increase drug absorption and conveyance. Using response
surface design, the formulated geniposide pharmacosomes were optimized and their attributes
examined by researchers . Phospholipid-to-drug ratio, temperature of the reaction mixture, and
concentration of drugs were 3:1, 50°C, and 5.5 mg / mL respectively.
• Pharmacosomes prepared for various anti- inflammatory medications, which are poorly soluble, non-
steroidal, i.e. Aceclofenac, Diclofenac, Aspirin, and Fenoprofen. These studies show that
pharmacosomes can enhance the ability to dissolve and permeate a substance. Drug permeation across
the skin also increased when tested with percutaneous in vitro absorption by using fenoprofen flow
through the diffusion cell.
• Isoniazid pharmacosomes have increased permeability and are targeting the macrophage.
• Pharmacosomes also enhance the biopharmaceutical properties of bioactive phytoconstituents,
including flavones, glycosides and xanthones.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

• Pharmacosomes can increase the permeation rate by improving the fluidity of the membranes.
The transition temperature of vesicles in the form of vesicles and micelles could have an obvious
effect on the vesicular interaction with the bio membrane, thus improving the transfer of drug across
the membrane.
• Pharmacosomes phase transition temperature in the vesicular and micellar state may have a major
effect on their membrane interaction and interact with bi membranes, thus allowing better transfer of
active ingredients. This interaction leads to changes in

the temperature of bio membranes in phase transition, thus improving the fluidity of the
membranes.
• The approaches have successfully improved therapy, performance, and various drugs such as pindolol
diglyceride, amoxicillin, taxol, cytarbin, dermatan sulfate, bupranolol hydrochloride, and so on.
• The process of injection of tetra hydro furan is the negatively charged pharmacosomal nanometer
Acyclovir succinyl glyceryl monostearate. They found that centrifugation and heating effect on
stability of pharmacosomes very weekly, whereas freezing and lyophilization disturbed the structure
of the pharmacosomes.
• Tetra hydro furan injection technique and concluded that in target tissue, pharmacosomes provoke
liver targeting and sustained release effect.

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2. LITERATURE REVIEW

Ali Gamal Ahmed Al-kaf et al., (2017) have developed different lipid based vesicular systems
as controlled and targeted drug delivery systems. Pharmacosomes are novel vesicular drug
delivery systems. They are potential alternative to conventional vesicles. Pharmacosomes are
the amphiphilic phospholipids complexes of drugs bearing active hydrogen that bind to
phospholipids. Similar to other vesicular systems pharmacosomes provide an efficient method
for delivery of drug directly to the site of infection, leading to reduction of drug toxicity with no
adverse effects. They also reduces the cost of therapy by improving bioavailability of medication,
especially in the case of poorly soluble drugs. This approach as a drug delivery system certainly
promises a reliable, safe, selective and precise method of drug delivery. They help in controlled
release of drug at the site of action as well as in reduction in cost of therapy, drug leakage
and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. They are
mainly prepared by hand-shaking and ether injection method. The Pharmacosomes have
evaluated for different parameters such as size, surface morphology and in vitro release rate. This
article reviews the potential of pharmacosomes as a controlled and targeted drug delivery
systems and highlights the methods of preparation and characterization.

Meenu Soman*, Prof. (Dr). Shaiju S Dharan, Litto T Mathew(2020) Pharmacosome is A

newer novel vesicular approach in the drug delivery system. It reduces toxicity, minimum dosage
Frequency and has drug entrapment efficiency. In the present research work, an attempt was made to
develop pharmacosomal Gel from pharmacosomal suspension for topical delivery containing non-
steroidal anti-inflammatory drug to treat rheumatoid Arthritis. This approach provides the sustained
release of drug and thereby reducing the Frequency of drug administration and Improves patient
compliance. Pharmacosomes were Prepared by thin film hydration technique/hand shaking method by
Using soya lecithin as Phospholipid in different ratios using different solvents. The prepared
pharmacosomes Were evaluated For preformualtion parameters. All batches of pharmacosomes were
Evaluated for entrapment efficiency, drug content and in Vitro drug release. After Evaluation the best
formulation was selected for the preparation of pharmacosomal gel. Pharmacosomal gel were prepared
by using carbapol 934 and triethanolamine. The prepared gel was evaluated for physical Appearance
and homogeneity, clarity, pH, viscosity, Spreadability, extrudability and drug diffusion data. The
study indicated that the pharmacosomal gel of etoricoxib follows sustained release mechanism. It
shows better drug release and high Entrapment efficiency. The pharmacosome could be prepared in a
Cost effective and simple manner.

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Priti et al., (2024) Miconazole nitrate, a potent antifungal agent, has been a cornerstone in
the treatment of these infections. However, its efficacy is hampered by limited skin
penetration and rapid clearance, necessitating frequent applications and potentially leading to
suboptimal outcomes. In response to these challenges, this study aimed to develop a novel
formulation utilizing pharmacosomes to encapsulate miconazole nitrate, thereby enhancing
its delivery and therapeutic effectiveness. Pharmacosomes, lipid-based vesicular carriers, hold
promise as advanced drug delivery systems due to their ability to improve drug solubility,
stability, and bioavailability. By entrapping miconazole nitrate within pharmacosomes, it is
hypothesized that its skin permeation and retention would be significantly enhanced, leading
to prolonged drug release at the site of infection and ultimately improved clinical outcomes.
The formulation process involved meticulous selection of phospholipids, cholesterol, and other
excipients to construct pharmacosomes encapsulating miconazole nitrate. Various methods such
as thin film hydration, ethanol injection, and solvent evaporation were explored to optimize the
formulation parameters and ensure uniform distribution of the drug within the vesicles.
Physicochemical properties including particle size, zeta potential, and drug encapsulation
efficiency were rigorously evaluated to ascertain the quality and stability of thepharmacosome
formulation. In conclusion, the formulation and evaluation of pharmacosome topical antifungal
gel of miconazole nitrate represent a significant advancement in the field of topical drug
delivery. By harnessing the unique properties of pharmacosomes, this formulation offers
improved drug delivery efficiency, sustained release, and enhanced therapeutic efficacy. Future
studies should focus on clinical trials to validate these findings and ascertain the clinical
utility of this innovative formulation in the management of fungal infections.

Katarzyna Trzeciak et al., (2023) The applicability of different solvent-free approaches leading
to the amorphization of active pharmaceutical ingredients (APIs) was tested. Ethenzamide (ET),
an analgesic and anti-inflammatory drug, and two ethenzamide cocrystals with glutaric acid
(GLU) and ethyl malonic acid (EMA) as coformers were used as pharmaceutical models.
Calcinated and thermally untreated silica gel was applied as an amorphous reagent. Three
methods were used to prepare the samples: manual physical mixing, melting, and grinding in
a ball mill. The ET:GLU and ET:EMA cocrystals forming low-melting eutectic phases were
selected as the best candidates for testing amorphization by thermal treatment. The progress and
degree of amorphousness were determined using instrumental techniques: solid-state NMR
spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. In each case, the
API amorphization was complete and the

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process was irreversible. A comparative analysis of the dissolution profiles showed that the
dissolution kinetics for each sample are significantly different. The nature and mechanism of this
distinction are discussed.

Naveen taj et al., (2022) The objective of the selected study was to develo p and statistically
optimize fluconazole (drug) loaded pharmacosomes (carrier) to enhance transdermal permeation
by incorporating into gel base and to treat fungal infections by selecting the Box-Behnken
model. Methods: Fluconazole is an antifungal drug which belongs to BCS class-II with high
permeability and choice for topical drug delivery. In the study, the levels of the lecithin (lipid),
dichloromethane and DMSO are selected as independent variables were varied to study the
influence on particle size, % entrapment efficiency and in vitro drug release as dependent
variables. Factorial designs through software Design expert version 13 (Box-Behnken design)
is applied for this study and the optimization process was carried out using the desirability plots
and point prediction techniques. Results: Results of the study with the application of a
design expert shows that the optimized drug-loaded pharmacosomes with vesicle size of
158.87±0.56 nm as predicted and zeta potential of-30.6mV indicating good stability of the
formulation, entrapment efficiency of 90.6±1.12% and in vitro drug release of 97.59±1.84%
respectively. The optimized formulation loaded into gel base and compared with the marketed
gel formulation. All the evaluation parameters confirmed that the physical mixture of drug and
excipients was compatible without any interactions. Conclusion: Through obtained results, it’s
concluded that; the independent variable plays a crucial role in optimizing formulation.
Study data provided strong evidence that the optimized vesicular formulation through Box-
Behnken factorial design can be potentially useful as a drug carrier for loading drug of selected
category for enhancing transdermal delivery.

Nachikethana C, Venkatesh(2024) Pharmacosomes are colloidal dispersions formed by Covalently

bonding drugs to lipids, combining the Greek Words for “drug” and “carrier.” They can take various
forms, Such as vesicular or micellar aggregates, and effectively Overcome limitations of traditional
systems like Transferosomes . Their amphiphilic nature reduces Interfacial tension, enhancing drug
bioavailability while Minimizing gastrointestinal toxicity and Suitable for both Hydrophilic and
lipophilic drugs, Pharmacosomes enable Controlled release and targeted delivery, reducing treatment
Costs and side effects. The unique properties of phospholipids allow for modified drug release Rates,
making pharmacosomes a promising strategy for improving therapeutic efficacy. Phospholipids
allow for modified drug release rates, making Pharmacosomes a promising Strategy for improving
therapeutic efficacy.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel
The research focused on creating Pharmacosomes with telmisartan to enhance its solubility,
bioavailability, and reduce Toxicity. Using soya phosphatidylcholine in varying ratios, the complex
was prepared via Solvent evaporation method. The optimized Formulation (F1, 1:1 ratio) achieved a
drug Concentration of 96.83% w/w. Characterization through X-ray powder diffraction Confirmed
complex formation, while scanning electron microscopy showed disc-shaped particles. In in vitro
dissolution Studies, F1 released 94.69% of the drug over ten hours, Compared to 60.42% for pure
telmisartan. These findings suggest that The phospholipid Complex significantly improves
telmisartan’s solubility and therapeutic potential.

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3. AIM & OBJECTIVE

Aim: To formulate and evaluate a Pharmacosomal gel containing Ethenzamide for enhanced
topical delivery, improved bioavailability, and sustained anti-inflammatory and analgesic
effects.
Objective

• To prepare a Pharmacosomal complex of Ethenzamide using appropriate phospholipids.

• To incorporate the Pharmacosomal complex into a topical gel base suitable for skin
application.
• To evaluate particle size, entrapment efficiency, and morphology of the Pharmacosomal
complex.
• To perform physicochemical characterization using techniques like FTIR and SEM.
• To assess the physical parameters of the gel such as pH, viscosity, spread ability, and
homogeneity.
• To evaluate the drug content and in vitro drug release profile of the gel.

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4. PLAN OF WORK

In this study the following works were carried out.

1. Selection of Ethenzemide pure drug.

2. Formulation of pharmacosomal gel containing Ethenzemide by solvent evaporation
technique.
3. Characterization of formulated pharmacosomes
a) Scanning electron microscopy (SEM).
b) Drug entrapment and loading capacity.
c) Fourier transform infrared spectroscopy (FTIR) analysis.
d) Size analysis and zeta potential.
4. Stability studies of the formulated Ethenzemide pharmacosomal gel.
5. In vitro drug release profile of the formulated Ethenzemide pharmacosomal gel and compare it
with the free dug solution.
6. Evaluation of results.

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5. DRUG PROFILE

Name: Ethenzamide
Structure:

IUPAC Name: 2-ethoxybenzamide

Chemical Formula: C9H11NO2

Molecular weight: 165 g/mol

Mechanism of Action: Ethenzamide, an analgesic and anti-inflammatory drug, primarily works

by inhibiting the synthesis of prostaglandins, which are chemicals that promote inflammation and
pain, through the blockade of the 5-hydroxytryptamine (5HT)2B receptor and, to a lesser extent,
by inhibiting cyclooxygenase (COX) enzymes.

Pharmacodynamics: Ethenzemide works by inhibiting cyclooxygenase (COX) enzymes,

primarily COX-2,Onset of action is typically within 30 to 60 minutes after oral
administration. Ethenzemide is less potent and has fewer gastrointestinal side effects
compared to some other NSAIDs. It has minimal sedative or CNS depressant effects.

Pharmacokinetics

Absorption: 90%

Volume of distribution: 0.5L/kg

Protein binding: 60-70%

Metabolism: Hepatic

Route of elimination: urine

Half-life : 2hrs

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Uses: Ethenzemide (2-ethoxybenzamide) is a common analgesic and anti-inflammatory drug that

is used for the relief of fever, headaches, and other minor aches and pains. It is also an ingredient
in cold medications and many prescription analgesics.

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6. EXCIPIENT PROFILE

PHOSPHOTIDYLCHOLINE

Chemistry

Lecithin in used for the study is composed of different type of phospholipids like
phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol and lysophosphatidic choline
cholesterol. The structure of basic phospholipids molecules given below.
Structure:

Fig-4:Structure of a phospholipid

Color: Yellowish brown

Molecular Formula : C36H72NO8P

MolecularWeight:677.93 gm

Consistency: Agglomerates

Iodine value: 85-95

Peroxide value: Not more than-3

Solubility:

Lecithin is soluble in both aqueous and organic phase. Hence it can be used as emulsifier in food industry
and it is also capable of forming vesicles there by it is used in pharmaceutical industry. It gives clear or
slightly opalescent solutions with both phases.

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CARBOPOL 934

Synonyms:
Carbopol, ACRYLIC ACID, CARBOPOL 940, CARBOPOL 910, CARBOPOL 934

IUPAC Name：Prop-2-enoic acid

Molecular Weight：102.133 g/mol

Structure:

Fig-5: Structure of Carbopol 934

Melting point: 95 °C

Description:
Polyacrylic acid (PAA) is hygroscopic, brittle and colorless in nature with Tg at nearly 106°C. At
temperatures above 200 to 250°C, it loses water and becomes an insoluble crosslinked polymer
anhydride. Solubility of dried PAA in water increases with rise in temperatures.
Polyacrylic acid (PAA) is a hydrophilic colloidal solution, similar in properties to water-soluble natural
gums. It is a clear, colorless, viscous stable solution. Applications include the modification of
aqueous formulations for such end uses as cleaners, binders, adhesives, and emulsion paints. The
sodium, potassium, and ammonium salts are effective thickeners and dispersants useful in both
natural and synthetic latex systems. PAA in ceramic applications improves dry strength, dispersant
action, and improved workability of the clays. PAA is stable to hydrolysis and is not susceptible to
bacterial degradation.
Chemical Properties:
Carbomers are white-colored, ‘fluffy’, acidic, hygroscopic powders with a characteristic slight odor.
A granular carbomer is also available (Carbopol 71G).

Uses:
carboxypolymethylene is a binder, film-former and emulsion stabilizer. It can also help increase
product viscosity.

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Pharmaceutical Applications:
Carbomers are used in liquid or semisolid pharmaceutical formulations as rheology modifiers.
Formulations include creams, gels, lotions and ointments for use in ophthalmic, rectal, topical and
vaginal preparations.

HYDROXYPROPYL METHYLCELLULOSE K15M (HPMC K15M)

Hydroxypropyl methylcellulose is a semisynthetic, inert, viscoelastic polymer used in many commercial

products as an excipient and controlled delivery part in oral medicaments. Hydroxypropyl
methylcellulose is a common ingredient in oral products; it's mostly used as a tablet binder, in film
wrapping, and as a matrix in extended-release tablet formulations.

Synonyms

HPMC K15M, (Hydroxypropyl)methyl cellulose K15M; Benecel MHPC; E464; HPMC; Methocel;
Hydroxypropyl methylcellulose; methyl hydroxypropylcellulose

Molecular formula: C56H108O30

Structural formula:

Fig-6: Structure of HPMC

Molecular weight: 1261.4 g/mol

Chemical name: Cellulose Hydroxy Propyl Methyl Ether

Appearance: Solid

Colour: White

Ash value: Its ash value is found in between 2–4%, this value may change with change in viscosity.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Moisture content

It can absorb moisture from the surrounding but it depends on how much initial moisture content
and humidity present in the atmosphere.

Solubility

Coldwater soluble, forming a viscous colloidal solution; practically insoluble in chloroform, ethanol
(95%) and ether, but soluble in ethanol and dichloromethane mixtures, methanol and
dichloromethane mixtures, and water-alcohol mixtures. In aqueous acetone solutions, mixtures of
dichloromethane and propane-2-ol, and other organic solvents, some grades of hydroxypropyl
methylcellulose are soluble.

Viscosity

A wide range of viscosity types is commercially available. While Hydroxypropyl methylcellulose is

most widely prepared as aqueous solutions, it can also be dissolved in aqueous alcohols such as ethanol
and propane-2-ol if the alcohol content is less than 50% w/w. To produce viscous hydroxypropyl
methylcellulose solutions, dichloromethane and ethanol mixtures can be used. Chemical solvents
produce more viscous solutions, and increasing concentration often creates more viscous solutions.

Functional category

Coating agent; film-former; rate-controlling polymer for sustained release; stabilizing agent; suspending
agent; tablet binder; viscosity increasing agent.
Stability

Hydroxypropyl methylcellulose powder is hygroscopic after drying but still is a stable material.
Solutions of HPMC are stable at pH 3–11. As the temperature increases, the viscosity of solutions
decreases. Upon heating and cooling, it undergoes a reversible sol-gel transformation, respectively. The
gel point is 50–90°C, depending upon the grade and concentration of the material.
Applications

Hydroxypropyl methylcellulose is widely used as an excipient in oral and topical pharmaceutical

formulations. While unnecessary oral intake can have a laxative impact, it is widely treated as a nontoxic
and non-irritant content.

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Storage

It should be stored in a well-closed container, in a cool, dry place.

METHANOL

Synonyms: Alcohol

Emperical formula: C H 3 OH

Structure:

Fig-6: Molecular structure of Methanol

Molecular weight: 32 g/mol

Applications: Methanol is highly toxic and unfit for consumption. At room temperature, it is a
polar liquid, and is used as an antifreeze, solvent, fuel, and as a denaturant for ethanol. It is also
used for producing biodiesel via trans esterification reaction

6. MATERIALS AND EQUIPMENTS

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Materials:
Table-1: List of chemicals used and supplier/Manufacturer names

[Link]
Materials MANUFACTURERS

1
Ethenzamide Synpharma Research Labs, HYD

2 soya lecithin Synpharma Research Labs, HYD

3 Synpharma Research Labs, HYD

Dichlorometane

4 Synpharma Research Labs, HYD

PEG

5 Methanol Synpharma Research Labs, HYD

6 Disodium hydrogen Synpharma Research Labs, HYD

orthophosphate

7 Potassium dihydrophosphate Synpharma Research Labs, HYD

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List of Equipment:

Table-2: Details of equipment’s used

S. NO INSTRUMENT MANUFACTURER

1 Electronic Balance Denver instrument

2 Digital Screw gauge Besto

3 Hot Air Oven Kshitij innovations, Ambala cantt

4 Magnetic Stirrer Cintex industrial corporation, Mumbai

5 Digital pH Meter Global pH meter

6 Ultra Sonicator Mrc laboratory equipment

7 UV Spectrophotometer Analytical lab

8 Heating mantle Sisco, thane, Maharastra

9 Rotary evaporator Scientific Aditya

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7. METHODOLOGY

Solubility studies
Ethenzamide is found to Soluble in Ethanol, Methanol and Slightly soluble in water.
Determination of melting point
Melting point of Ethenzamide was measured by capillary method.
Determination of λmax
100 mg of Ethenzamide was dissolved in 10 ml of methanol and further diluted with pH 7.4 buffer,
suitable dilutions were made and finally scanned for maximum absorbance using UV spectrophotometer
in the range from 200 to 400 nm. Average of triplicate readings was taken.
Estimation of Ethenzamide
In present study, the spectrophotometric method was adopted for the estimation of Ethenzamide
using U.V. spectrophotometer.
Compatibility study (IR spectroscopy)

FTIR analysis was performed in order to study the compatibility of ingredients used in the
preparation of nanoparticles, using a Shimadzu FTIR spectrophotometer (Prestige21, Shimadzu
Corporation, Kyoto, Japan). Atomoxetine and Excipients their mixture with ratio (1:1) was evaluated
using FTIR spectrophotometer using potassium bromide disc technique where 1mg of the sample is
mixed with 100 mg of dry powdered KBr; the mixture is pressed into a transparent disc and was
inserted in the apparatus for IR scan.

Preparation of standard curve of Ethenzamide in 7.4 pH buffer

Utilizing a solution made in a 7.4 pH buffer and a UV/visible spectrophotometer set to 246 nm,
Ethenzamide was examined.
Preparation of 7.4 pH
2.48 gm of Disodium hydrogen phosphate and 0.19 gm of potassium dihydrogen phosphate and 8
gm of sodium hydroxide in 1000 ml of water.

Preparation of standard curve of Ethenzamide in 7.4 pH

Ethenzamide 10 mg was precisely measured and diluted in 10 ml of 7.4 phosphate buffer for the standard
graph. Using 7.4 phosphate buffer, several concentrations of Ethenzamide 10, 20, 30, 40, and 50
mcg/ml were produced from the stock solution (100ppm).

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Table-3: Composition of Ethenzamide Pharmacosomes (F1 to F4)

Procedure
Solvent Evaporation Technique
Dissolve Ethezamide and phosphatidylcholine in chloroform: methanol (1:1). Allow the reaction to
proceed for 3-.4 hours at room temperature or under mild heating (4050°C). Filter to remove by-
products like dicyclohexylurea (DCU), and evaporate solvents to recover the conjugate. Transfer the
purified drug-lipid conjugate into a round-bottom flask. Evaporate the solvent using a rotary evaporator
at 40–50°C under reduced pressure. A thin lipid film forms on the inner wall of the flask. Hydrate the
dry lipid film using phosphate buffer (pH 7.4) or distilled water. Agitate using a magnetic stirrer
or vortex mixer for 30–60 minutes. This leads to self-assembly of the conjugates into
pharmacosomes. Sonicate the suspension using a probe or bath sonicator for a few minutes to reduce
particle size and obtain uniform vesicles.

GEL PREPARATION

Table-4: Composition of Ethenzamide Pharmacosomal gel (F1 to F4)

Ingredients (mg)
S. No. F1 F2 F3 F4

1 Pharmacosomal gel 5 5 5 5

2 HPMC 250 500 - -

3 Carbopol 934 - - 500 1000

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CHARACTERIZATION

The incorporation of the Ethenzamide loaded Pharmacosomes into separate gels was achieved by slow
mechanical mixing at 25 rpm for 10 minutes. The optimized formulation was incorporated into different
gelling agent concentration.

Determination of pH:

The value of pH of Pharmacosomal gel was measured by using digital pH meter (Lab India Sab
5000 pH meter) at the room temperature.

Spread ability
Place a fixed amount of Pharmacosomal gel (usually 0.5 g) in the center of the bottom glass slide.
Gently place the second glass slide on top of the gel, ensuring no air bubbles are trapped. Place a weight
on top of the upper slide. Allow the weight to sit for a fixed time (usually 5 minutes). Remove
the weight carefully. Measure the diameter of the spread gel using a ruler or caliper in two perpendicular
directions, and calculate the average.

Spread ability(S)=M×L/T
where:

M = weight tied to the upper slide (g)

L = length moved by the slide (cm)

T = time taken (sec)

Viscosity

The measurement of viscosity of the prepared gel was done using Brookfield digital Viscometer.
0
The viscosity was measured using spindle no. 6 at 10 rpm and 25 C. The sufficient quantity of gel
was filled in appropriate wide mouth container. The gel was filled in the wide mouth container in
such way that it should sufficiently allow to dip the spindle of the Viscometer. Samples of the gels
were allowed to settle over 30 min at the constant temperature (25 ±/10C) before the measurements.
Entrapment efficiency
To 0.2 g of Pharmacosomal gel, weighed in a glass tube, 10 ml phosphate buffer pH 7.4 were
added. The aqueous suspension was then sonicated. Pharmacosomal gel containing Ethenzamide were
separated from unentrapped drug by centrifugation at 9000rpm for 45 min at 4⁰C. The supernatant was
recovered and assayed spectrophotometrically using Spectrophotometer.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel
The encapsulation percentage of drug (EP) was calculated by the following equation
EP = [(Ct – Cr)/ Ct] * 100

Where:

Ct = Concentration of total Ethenzamide,

Cr = Concentration of free Ethenzamide

In Vitro Drug release study

The release studies were carried out in 10 ml Franz diffusion cell containing 10 ml Phosphate buffer.
Phosphate buffer pH 7.4 (10ml) was placed in a 10 ml beaker. The

beaker was assembled on a magnetic stirrer and the medium was equilibrated at 37±5 0C. Dialysis
membrane was taken and one end of the membrane was sealed. After separation of non-entrapped
Ethenzamide Pharmacosomal was filled in the dialysis membrane and other end was closed. The
dialysis membrane containing the sample was suspended in the medium. 1ml of aliquots were withdrawn
at specific intervals, filtered after withdrawal and the apparatus was immediately replenished with same
quantity of fresh buffer medium.

Stability Studies
The formulations stored in glass vials covered with aluminum foil were kept at room temperature
and in refrigerator (4⁰C) for a period of 6 months, samples were withdrawn and hydrated with phosphate-
buffered saline (pH 7.4) and observed for any sign of drug crystallization under optical microscope.
Furthermore, the samples were also evaluated for particle size and percent retention of Ethenzamide.

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9. RESULTS AND DISCUSSION

In the present study 4 formulations with variable concentration of lipids were prepared and
evaluated for physico-chemical parameters, in vitro release studies and stability studies.

Preformulation studies:
Organoleptic evaluation:

Table-5: Organoleptic properties of Ethenzamide

Properties Results

Description Crystalline Powder

Taste Tasteless

Odor Odorless

Colour White to off-white crystalline

powder

Determination of Melting point:

Melting point of Ethenzamide was found in the range of 215-2170c, which complied with the standard,
indicating purity of the drug sample.

Solubility:

Ethenzamide is found to Soluble in Ethanol, Methanol and Slightly soluble in water.

Preparation of standard curve of Ethenzamide :

Standard curve of Ethenzamide was determined by plotting absorbance V/s concentration using
phosphate buffer pH 7.4 at 246 nm. And it follows the Beercs law. The R 2 value is 0.997.

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Table-5: Calibration curve of Ethenzamide in 7.4 phosphate buffer

Concentration (µg/ml) Absorbance

0 0

10 0.164
20 0.256
30 0.379
40 0.469
50 0.586

Fig-8: Calibration curve of Ethenzamide

Standard curve of Ethenzamide in 7.4 pH phosphate buffer as shown. Wavelength of maximum

absorption was found to be 246 nm. The Ethenzamide obeyed the Lambert-Beer’s law in concentration
range of 10-50μg/ml.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Drug - excipient compatibility studies (FT-IR):

The compatibility between the drug and the selected lipid and other excipients was evaluated using FTIR
peak matching method. There was no appearance or disappearance of peaks in the drug-lipid mixture,
which confirmed the absence of any chemical interaction between the drug, lipid and other chemicals.
Compatibility studies were performed using IR spectrophotometer. The IR spectrum of Pure drug
and physical mixture of drug and excipients were studied. The characteristic absorption of peaks
was obtained as above and as they were in official limits (±100 cm-1) the drug is compatible with
excipients.

EVALUATION PARAMETERS:
pH and Viscosity

Table-8: pH and Viscosity values of all formulations

[Link] pH Viscosity (cps)

F1 6.1 152
F2 5.9 148
F3 6.2 147
F4 6.5 155

Spread ability

Table-9: Spread ability values of all formulations

F. code Spread ability ([Link]/sec)

F1 4.75
F2 4.82
F3 4.86
F4 4.25

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Entrapment Efficiency:

Entrapment efficiency was determined by measuring the concentration of unentrapped free drug in
aqueous medium. About 1 ml of the drug loaded pharmacosomes dispersion was placed in the Eppendorf
tubes and centrifuged at 17000 rpm for 30 min. The pharmacosomes along with encapsulated drug were
separated at the bottom of the tubes. Plain pharmacosomes without drug was used as blank sample
and centrifuged in the same manner. In order to measure the free drug concentration, the UV absorbance
of the supernatant was determined at 246 nm.

Table-10: Drug entrapment efficiency

F. code Drug entrapment efficiency

F1 80.12
F2 78.91
F3 81.36
F4 75.98

Fig-11: Drug entrapment efficiency of all formulation

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Determination of Vesicle morphology and Size

The morphological characteristics of formulated pharmacosomes were carried by using Scanning

electron microscopy (SEM). A small drop of Pharmacosomal gel was placed between two rivets
fixed on a gold plated copper sample holder. The whole system was slushed under vacuum in liquid
nitrogen. The sample was heated to -850C for 30 min to sublime the surface moisture. Finally the sample
was coated with gold and allowed the SEM to capture the images at a temperature of - 1200c and voltage
of 5kV.

Fig-12: Particle size analysis of Optimized Pharmacosomal gel

Zeta potential

Fig-13: Zeta potential of Pharmacosomal gel

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Table-11: Evaluation Studies of particle size and Zeta potential Pharmacosomal gel

F. No Particle size (nm) Zeta potential

F1 119 -35
F2 128 -40
F3 133 -41
F4 126 -37

SEM Analysis

Fig-14: SEM Analysis of Pharmacosomal gel

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

In Vitro drug release studies:

Fig-12: In Vitro drug release studies of (F1-F4) formulation

Time F1 F2 F3 F4
0 0 0 0 0
1 26.39 24.10 27.84 25.31
2 32.28 31.28 34.12 32.42
3 45.83 44.17 47.86 46.17
4 55.10 53.29 57.19 54.75
5 67.58 64.37 68.25 68.12
6 75.83 73.08 75.83 78.10
7 82.90 83.41 85.17 84.56
8 94.38 95.10 97.82 95.82

Fig-15: In Vitro drug release studies of (F1-F4) formulation

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Mean % drug release

Time
[Link] Physical Ethenzamide
in changes
days 250C/60% 30°C/75°/° 400C/75%

1 01 No Change 97.82 96.45 95.82

2 30 No Change 97.82 96.51 95.24

3. 60 No Change 97.82 96.37 95.18

4. 90 No Change 97.82 96.28 95.10

Table-13: Stability studies of optimized formulations

Stability studies:

There was no significant change in physical and chemical properties of the Pharmacosomal gel
formulation F-3 after 3 months. Parameters quantified at various time intervals were shown. Optimized
formulations F3 was selected for accelerated stability studies as per ICH guidelines.

DISCUSSION

Particle size and zeta potential of the pharmacosomes were measured by photon correlation
spectroscopy using a Malvern Zetasizer and entrapment efficiency was determined by measuring the
concentration of unentrapped free drug in aqueous medium by Spectrophotometer. Zeta potential of
optimized pharmacosomel formulation was found -40 mV. Prepared gel of pharmacosome loaded with
Ethenzamide was prepared and evaluated for viscosity, pH, % drug content, spread ability and drug
release study. It was found that viscosity of prepared gel was 147 cps, pH was 6.2, % Drug entrapment
efficiency was 81.36 and spread ability was found as 4.86 ([Link]/sec)respectively. In Vitro drug
release from pharmacosomes was examined using Franz diffusion cell method and found 97.82 % in
8h. It was due to the release of free drug present in bag after leaching from pharmacosomes. Drug release
from pharmacosomal formulation was found in very sustained and controlled manner.

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 Formulation and Evaluation of Ethenzamide pharmacosomal gel

10. CONCLUSION

The present study was aimed for preparation of Ethenzamide pharmacosomal [Link]
pharmacosomal gel was prepared by Solvent Evaporation Technique. Pharmacosomes were
prepared by Solvent evaporation method and optimized on the base of average vesicle size and
% drug entrapment. The optimized formulation was further incorporated with gel base (Carbopol
gel) and characterized for their viscosity, pH, % Drug content, extrudability, spread ability, and
drug release study. The prepared four formulations were evaluated for various parameters. Among
the various formulation, the combination F3 was found to be most suitable because of high
encapsulation efficiency with smaller particle size. The formulation F3 comprising
phosphatidylcholine fulfills the requirement of good pharmacosomal gel formulation. In vitro drug
release up to 8 hours and 97.82 % drug was released. A higher Ethenzamide entrapment was
observed. It can be concluded that prepared gel containing Ethenzamide-loaded pharmacosomal
formulation was optimized and successfully formulated in the gel form can be of use for topical
preparation for its anti-inflammatory action.

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11. REFERENCES

1. Thakur Sonam, Tibrewal Richa, Pharmacosomes: An Overview, international journal of

Pharmaceuticals and Biological science archive,2017; 5(2): 1-7.
2. Jangam Payal R, Thombre Nilima A, Gaikwad Pallavi N. A Review: Proniosomes as a Novel
Drug Delivery System Asian J. Pharm. Tech. 2017; 7 (3): 166-174.
3. Sonam Ranga, Amit Kumar., A Review on Pharmacosomes. Research and Reviews: Journal
of Pharmaceutics and Nanotechnology, 2014; 2(1): 8-14
4. Selvaraju K., Vengadesh Prabhu K., Karthick K., Padma Preetha J. and Arul Kumaran K.S.G.
Pharmacosomes- An Immense Potential Vesicular Constructs Research J. Pharma. Dosage Forms
and Tech. 2011; 3(3): 84-86.
5. Nagasamy V. D, Kalyani K, Tulasi K, Swetha P, Shaik A. A, et alPharmacosomes: a potential
vesicular drug delivery system, International Journal of Pharmaceutical Science and Drug
Research. 2014; 6(2): 90-94.
6. Pavan Kumar, Debnath S, Babu N “Pharmacosomes as a novel vesicular drug delivery system”,
Int J of Novel Trends in Pharm. Sci.2013; 3(3): 46- 52.
7. D. Nagasamy Venkatesh, K. Kalyani, K. Tulasi, V. Swetha Priyanka, Shaik Abid Ali, S.
Shashi Kumar, et alPharmacosomes: A Potential Vesicular Drug Delivery System;
International Journal of Pharmaceutical Sciences and Drug Research 2014; 6(2): 91-92
8. PreetiKhulbe, Deepa Mohan Rajput, Tahseen Khan et alPharmacosomes: An Effective Approach
for Drug Delivery; SGVU Journal of Pharmaceutical Research and Education, 2019; 4(1):
352-358
9. Mantelli S, Speiser P, Hauser H. Phase behaviour of a diglyceride prodrug: spontaneous
formation of unilamellar vesicles Chem. Phys Lipids 1985; 37: 329–343.
10. P. H. Sharma, P. V. Powar, S. S. Sharma Pharmacosomes: A novel drug delivery system; The
Pharma Innovation Journal 2014; 3(10): 94-100
11. Drug carrier Wikipedia, sevenson, sonke, carrier based drug delivery, 2004.
12. Biju SS, Talegaonkar S, Mishra PR, Khar KR. Vesicular System: An overveiw. Indian
J. Pharm Sci, 2009; 71(4): 421-427.
13. Bommala Supraja, Saritha Mullangi, An updated review on pharmacosomes, a vesicular drug
delivery system, Journal of Drug Delivery and Therapeutics. 2019; 9(1s): 393-402
14. Solanki D, Patidar A, Kukde D, Pharmacosomes – A Review, International Journal of
Pharmacy, Eng and Life Sci. 2016; 12(3): 70-78.

Dept of Pharmaceutics Page 38

 Formulation and Evaluation of Ethenzamide pharmacosomal gel

15. Lawrence MJ. Surfactant Systems: Their use in drug delivery. Chem Soc Rev, 1994; 23: 417–
424.
16. Muller-Goymann CC, Hamann HJ. Pharmacosomes: Multilamellar vesicles consisting of pure
drug. Eur J Pharm Biopharm, 1991; 37: 113–117.
17. A. Singh and R. Jain, “Targeted Vesicular Constructs for cryoprotection and treatment of H.
Pylori infections,” US Patent 6576, 2003, 625.
18. Kolar kusuma, D. Priyanka, J. Sundaraseelan. Formulation and evaluation of pharmacosomal gel
loaded with NSAID. WJPMR2018; 4 (7): 81-88.
19. Semalty A, Semalty M, Rawat BS, Singh D, Rawat MSM. Development and characterization of
aspirin- phospholipid complex for improved drug delivery. IJPS 2010; 2(2): 940-947.
20. Semalty A, Semalty M, Rawat B S, Singh D, Rawat MSM. Development and evaluation of
pharmacosomes of aceclofenac. IJPS 2010;72: 576-81.
21. Kamalesh M, Baviskar D, Wagh K, Baviskar K. Formulation and evaluation of pharmacosomes
of Ketoprofen. Indo Am J Pharm Res. 2014; 4(3): 1363-1368.
22. Raikhman L M, Ivanov V E, Moshkovskii Y S. Development of Ibuprofen pharmacosomes
for enhancing the bioavailability. Drug Dev Indian Pharm. 2002; 28(5): 473-482.
23. Letha S, Shammika P, Viswanand V. Formulation and evaluation of etodolac pharmacosomes: A
novel approach towards rheumatoid arthritis. IJPT 2017; 9(2): 29665-29680.
24. Semalty A, Semalty M, Rawat BS, Singh D, Rawat MSM. Development and physicochemical
evaluation of pharmacosomes of diclofenac. IJPS 2010; 59: 335-344. 25. Raval, Madhabhai
M. Patel Techniques to Improve Bioavailability of Poorly Water Soluble Drugs – A review Amit
J. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 182-192.
26. Supraja, S. Mulangi: An updated review on pharmacosomes, a vesicular drug delivery
system. J. Drug Deliv. Ther. (2019) 9(1-s): 393-402.
27. Sreedevi, A. Swetha, C. Meenakshi, B. Rohit: Pharmacosomes-A review. Int. J. Pharm. Sci. Res.
(2012) 12(1): 114-117.
28. M. D. Hussain, S. Mirza, I. Miroshnyk, M. J. Habib, J. F. Brausch, : Enhanced dissolution
and oral bioavailability of losartan formulation: Modulating effect of phospholipids.
Pharmaceutics (2010) 2: 339-350.
29. Semalty, M. Semalty, B. S. Rawat, D. Singh, M. S. M. Rawat,: Development and
physicochemical evaluation of pharmacosomes of diclofenac. Acta Pharm. (2009) 59(3): 335-
344.
30. Jam, F. A., Rauf, A. S., Husnain, I., Bilal, H. Z., Yasir, A., & Mashood, M. (2014).

Dept of Pharmaceutics Page 39

 Formulation and Evaluation of Ethenzamide pharmacosomal gel

Identify factors affecting the management of political behavior among bank staff. African Journal
of Business Management, 5(23), 9896-9904
31. M. Kamalesh, D. Baviskar, K. Wagh, K. Baviskar, : Formulation and evaluation of
pharmacosomes of ketoprofen. Indo Am. J. Pharm. Res. (2014) 4(3): 1363-1368.
32. Y. Gong, W. Liu, X. Huang, L. Hao, Y. Li, S. Sun, : Antifungal activity and potential mechanism
of N-butylphthalide alone and in combination with fluconazole against Candida albicans. Front.
Microbiol. (2019) 10: 1461.
33. Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of
drugs: reviewing three decades of research. Int J Pharm. 2007 Mar 6;332(12):1-16.
34. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes-novel vesicular carriers for
enhanced delivery: characterization and skin penetration properties. J Control Release. 2000 Apr
3;65(3):403-18. doi: 10.1016/s0168-3659(99)00222-9, PMID 10699298.
35. Monti D, Egiziano E, Burgalassi S, Tampucci S, Terreni E, Tivegna S, Chetoni P. Influence of a
combination of chemical enhancers and iontophoresis on in vitro transungual permeation of
nystatin. AAPS PharmSciTech. 2018 May;19(4):1574-
81.
36. Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shafique S. Effective use of
nanocarriers as drug delivery systems for the treatment of selected tumors. Int J
Nanomedicine. 2017 Oct 5;12:7291-309.
37. Semalty A, Semalty M, Rawat BS, Singh D, Rawat MS. Pharmacosomes: the lipidbased new
drug delivery system. Expert Opin Drug Deliv. 2009 Jun;6(6):599-612.
38. Kasar PM, Kale K, Phadtare DG. Formulation and evaluation of topical antifungal gel containing
itraconazole. Int J Curr Pharm Sci 2018;10(4).
39. Raphael AP, Garrastazu G, Sonvico F, Prow TW. Formulation design for topical drug and
nanoparticle treatment of skin disease. Ther Deliv. 2015 Feb;6(2):197-216.
40. El-Housiny S, Shams Eldeen MA, El-Attar YA, Salem HA, Attia D, Bendas ER. Fluconazole-
loaded solid lipid nanoparticles topical gel for the treatment of pityriasis versicolor: formulation
and clinical study. Drug Deliv. 2018 Nov;25(1):78-90.
41. NiyazBasha B, Kalyani P, Divakar G. Formulation and evaluation of gel containing fluconazole-
antifungal. Int J Drug Dev Res. 2011;3:109-12.
42. Hardikar SR, Mulla SS. Optimization of formulation of solid dispersion of furosemide by factorial
design. Int J Pharm Pharm Sci. 2020 Apr;12(4):43-8.

Dept of Pharmaceutics Page 41

 Formulation and Evaluation of Ethenzamide pharmacosomal gel

43. Yue PF, Zheng Q, Wu B, Yang M, Wang MS, Zhang HY. Process optimization by response
surface design and characterization study on geniposide pharmacosomes. Pharm Dev Technol.
2012 Jan-Feb;17(1):94-102.
44. Gupta N, Jain S. Designing and optimization of naproxen sodium deformable vesicular
systems through factorial design: box behenken model. Int J App Pharm. 2021;13:190-
7.
45. Deka T, Das MK, Das S, Das P, Singha LR. Box-behnken design approach to develop nano-
vesicular herbal gel for the management of skin cancer in an experimental animal model. Int J
App Pharm. 2022;14(6):148-66.

Dept of Pharmaceutics Page 41