MSC PHARMACEUTICAL SCIENCE

DRUG DOSAGE FORM AND DESIGN

PLM 341

ASSESSMENT C2- ESSAY 3 OF 3

SUBMITTED TO: MADAM RANJIT BARRY

NAME: BILAL ASGHAR

STUDENT ID: 2309354

SESSION: 2023-2024
PHYSICOCHEMICAL FACTORS AFFECTING DRUG FORMULATION

Particle size impacts the formation of effective and safe medicines (Taylor 2018). It

affects the bioavailability of poorly soluble drugs. Suppose the particle size changes from

23.5 μm either increased or decreased. In that case, it will affect the bioavailability by

impacting the surface area (Ashford 2018). Still, here, our drug particle size is smaller,

and we may or may not need to change the size of particles because of the capsulation

of the drug. Pka value will affect the solubility of the drug in an aqueous medium.

Moreover, compounds at different pH levels influence the absorption, distribution,

metabolism, excretion, and toxicity of a drug (Manallack et al. 2012). The weak acidic

drug having Pka 7.5 is un-ionised chiefly in the stomach at PH 1.2 and almost ionised in

the intestine at PH 6.8, so the weak acidic drug is better absorbed in the stomach where

it is un-ionized (Ashford 2018). The drug formulation is thermodynamically unstable due

to the metastable polymorph form; moreover, these metastable polymorphs are

physically more stable than chemical stability They can also be transformed into low-

energy and thermodynamically stable forms (Raza et al. 2014). The drug can be said to

be highly soluble when its highest dose is dissolved in an aqueous medium having the PH

range 1 to 8, and the drug can be said to be highly permeable when 90 per cent of the

dose is absorbed when it is administered (Ashford 2018). The solubility of the drug

formulation will be low as it is less soluble and highly permeable because it falls in the

BCS 2 classification. (Dahan, M. Mille and Amidon 2009).

PHYSIOLOGICAL FACTORS AFFECTING DRUG FORMULATION

(Ashford 2018). The physiological factors that affect the formulation include the following

parameters: gastrointestinal juices, bile salts, food, gastric emptying time, and liver

metabolism. The absorption of drugs, especially for poor soluble drugs, depends on the

amount of gastric juices inside GIT. Another factor affecting drug formulation is the

presence of bile salts, which enhance the solubility of poorly water-soluble drugs via

micellar solubilisation. The BCS class 2 drug dissolution depends upon the presence of a

medium consisting of bile salts. Moreover, the gastric emptying time also impacts drug

absorption, and the rate at which the stomach becomes empty will affect the plasma

concentration profile. Food intake increases the PH and slows the gastric empty time,

and elevation of gastric pH following a meal may enhance the dissolution of a weak acid.

Lastly, the liver is the final barrier to metabolising drugs through the first-pass effect.

Mostly, some drugs are so extensively metabolised by the liver that only a small amount

of the drug can reach systemic circulation. As a result, low bioavailability of that drug will

occur (Ashford 2018). The metabolism in the liver is affected due to age because of the

decline of enzymes and hepatocyte activity, any disease which causes reduced blood

supply towards the liver, genetic deficiency or drug interactions (Liu, Song and Zhang

2004).

CHOICE OF DOSAGE FORM AND FORMULATION

The choice of dosage form will be hard gelatin capsules to mask the bitter taste of the

drug. For the choice of formulation, we will replace emcompress the tribasic calcium

phosphate diluent mixture with hydrophilic diluent lactose anhydrous (Medicine

Complete 2023). The rationale for changing the formulation of the drug is to address

shortcomings like solubility, absorption, metabolism, and distribution of the drug (Ashford

2018).

CHANGES NEEDED IN FORMULATION

sodium or potassium this drug because it will form a layer around the drug to prevent it

from degradation in the stomach's acidic environment and act as a buffer layer.

Furthermore, it ensures dissolution occurs in the small intestine. The solubility of drugs

like weakly acidic drugs increases as the PH increases. Moreover, diluent emcompress is

lipophilic in nature (Medicine Complete 2023) and is replaced by hydrophilic diluent

because a lipophilic drug containing a hydrophilic diluent can increase the rate of

dissolution as the diluent will dissolve in GI fluid and spaces between drug particles

formed. The water will penetrate between the drug particles. As a result, dissolution will

increase. If the diluent emcompress is used, which is lipophilic in nature with a drug

having a log p of 6.2, the particles will stick together, a compact mass will form, and the

dissolution will only occur around the outside of the particles. Furthermore, there is a

chance that the drug particles face metabolism and biliary clearance issues (Ashford

2018). Moreover, the polymorphic form of the drug has shown that there will be side

effects on GI during the clinical trials, so to protect GI from drug side effects, the hard

gelatin shells will be coated with gastro-resistant material like carboxylic groups

containing polymers HPMC-AS (Hydroxy Propyl Methyl Cellulose acetate succinate) as

this material is water insoluble in an acidic environment. The formulation used to form

acid-resistant capsules is an aqueous solvent, gellan gum, and polymers, forming a film

around capsule shells. A double-dip moulding manufacturing process is used to

manufacture gastric-resistant capsules. The dosage form will remain the same as

selected with modifications due to the properties of a drug and diluent, such as

lipophilicity, and the drug is weakly acidic in nature, having different physicochemical

and physiological characteristics (Capsugel Belgium NV, Bornem 2014).

REFERENCE LIST:

Ashford, M., 2018. Bioavailability-physiochemical and dosage form factors. In: M. Aulton

and K. Taylor, eds. Aulton’s Pharmaceutics. Fifth. New York: Elsevier. pp. 320-335.
Capsugel Belgium NV, Bornem (BE), 2014. Acid resistant capsules. United States Patent
US 8,852,631B2 Oct 7, 2014.

Dahan, A. et al., 2009. Prediction of Solubility and Permeability Class Membership:

Provisional BCS Classification of the World’s Top Oral Drugs. The AAPS JOURNAL, 11, pp.

740–746.

Liu, Song and Zhang., 2004. Overview of factors affecting oral drug absorption. Asian

Journal of Drug Metabolism and Pharmacokinetics, 4(3), pp 167-176.

Manallack, D.T. et al., 2012. The significance of acid/base properties in drug discovery.

Royal Society of Chemistry, 42(2), pp, 485-496.

Raza, K. et al., 2014. Polymorphism: The Phenomenon Affecting the Performance of

Drugs. SOJ Pharm Pharm Sci, 1(2), pp, 1-10.

ROYAL PHARMACEUTICAL SOCIETY, 2023. Pharmaceutical excipients. [online]. London:

Pharmaceutical press. Available from: [Link]

[Link]/#/content/excipients/1001934973?hspl=tribasic&hspl=calcium

%20phosphate [Accessed 1 December 2023].

Taylor, K. M.G., 2018. Particle size analysis. In: M. Aulton and K. Taylor, eds. Aulton’s

Pharmaceutics. Fifth. New York: Elsevier. pp. 140-151.