Polymers in Oral Modified
Release Systems
Oral administration is the preferred route for drug delivery,
comprising 40% of all drug products in USP 27. To achieve optimal
therapeutic outcomes, delivery systems must be programmed to
release predetermined amounts of drug and remain at desired
gastrointestinal locations for complete absorption. This requires
controlling both drug release rate and system residence time within
the gastrointestinal tract.
Pharmaceutical excipients, particularly polymers, play a crucial role in
developing modified release oral drug delivery systems. These
polymers can be used to design matrix systems or membrane-
controlled release systems, each offering unique advantages for
controlling drug delivery.
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Matrix vs. Membrane-Controlled Systems
Matrix Systems Membrane-Controlled Systems
Utilize hydrophilic polymers and erodible polymers to Employ water-insoluble or enteric polymers as coating
form swellable and erodible matrices that control drug materials to modulate the rate or timing of drug release.
release through diffusion and erosion mechanisms.
• Osmotic pumps: Cellulose acetate, ethylcellulose
• Hydrophilic systems: Methylcellulose, HPMC, alginate, • Coated tablets: Poly(meth)acrylates, cellulose derivatives
chitosan
• Coated pellets: Ethylene vinyl acetate copolymer
• Erodible systems: Stearic acid, waxes, stearyl alcohol
• Insoluble systems: Polyethylene, polypropylene
Chitosan: A Versatile Natural
Polymer
Structure and Properties pH-Dependent Solubility
Chitosan is a poly(amino As a weak base with pKa of
saccharide) produced by 6.2-7.0, chitosan exhibits pH-
partial alkaline deacetylation of dependent solubility, dissolving
chitin. It's a linear, binary easily at low pH and becoming
heteropolysaccharide with insoluble at higher pH ranges.
amino and hydroxyl groups This property enables targeted
that can be chemically drug delivery.
modified for versatility.
Pharmaceutical Applications
Used in polymeric beads, tablets, floating microspheres, and colon-
specific capsules for controlled release of various drugs including
theophylline, insulin, and antibiotics.
Chitosan's Bioadhesive Properties
Enhanced drug targeting
Site-specific delivery to intestinal tissues
Protein protection
Shields proteins from enzymatic degradation
Absorption enhancement
Opens tight junctions between epithelial cells
Mucoadhesion
Interacts with negatively charged mucin layers
Protonated chitosan can interact with negatively charged mucin layers on mucosal tissues or cell membrane proteoglycans. This
bioadhesion process leads to increased contact between drugs and mucosal tissues with minimal and reversible membrane damages
compared with other agents such as bile acids and surfactants.
Alginate: Marine-Derived Polysaccharide
Chemical Structure
Natural Source
Composed of β-D-mannuronic acid,
Extracted from brown seaweed and
α-L-guluronic acid, and interspersed
found in some soil bacteria
M and G units
pH Sensitivity Gelation Properties
Shrinks at low pH and swells at Forms hydrogels with divalent
higher pH values cations like Ca²⁺ and Zn²⁺
Alginate's ability to rapidly form viscous solutions in contact with aqueous media and to form gels in contact with acid or
di- or trivalent cationic ions makes it ideal for use as a hydrophilic matrix in oral controlled release dosage forms.
Alginate Applications in Drug Delivery
Microparticles Cell Encapsulation Matrix Tablets
Alginate microparticles have been Alginate can microencapsulate cells Alginate shows good compressibility
investigated for loading both small to protect cellular integrity. Such and tablets composed of alginate
molecules and macromolecules. encapsulated cells can be used as microparticles have been widely
Particles smaller than 3μm can be carriers for peptide drugs and for oral investigated for oral controlled
absorbed via Peyer's patches, making immunization of ruminants. delivery, showing good mechanical
them useful for targeted delivery. properties and sustained release.
Pectins: Plant-Derived Polysaccharides
Natural Source
Extracted from plant cell walls, especially citrus peels and apple pomace
Chemical Structure
Complex polysaccharide of esterified D-galacturonic acid residues
Enzymatic Degradation
Degraded by pectinase enzymes abundant in the colon
Pectins form gels in acidic media or by cross-linking with calcium ions. The gelation characteristics depend on their
structure, with high-ester pectins gelling at low pH and high solid content, while low-ester pectins gel with calcium ions.
This versatility makes pectins excellent candidates for controlled release systems.
Hydroxypropyl Methylcellulose
(HPMC)
Powder Properties
White or light gray pellet or fibril powder, odorless and tasteless
Hydration
Swells to form a clear or slightly muddy colloid solution in cold water
Gel Formation
Forms a hydrated viscous layer that acts as a barrier to drug release
Drug Release
Controls release through diffusion and erosion mechanisms
HPMC is a soluble methylcellulose ether used as a thickening agent, binder, film former,
and hydrophilic matrix material. Available in various viscosity grades (4,000-100,000
mPa·s), it offers excellent control and reproducible drug release profiles through
manipulation of its chemical and physical properties.
HPMC Applications in Drug Delivery
Matrix Systems
HPMC matrices show sustained release through diffusion and erosion of the gel layer.
The viscosity of the polymer affects the diffusion pathway, allowing control of both
hydrophilic and hydrophobic drugs.
Buccal Delivery
Buccal adhesive tablets and films composed of HPMC show good buccal retention and
controlled release characteristics, suitable for drugs subject to first-pass metabolism.
Gastroretentive Systems
Mixtures with polymers like Carbopol 934 produce floating delivery systems that can
remain buoyant for up to 24 hours while providing controlled drug release.
Colon Delivery
Used in time-, pH-, and enzyme-controlled colonic drug delivery systems, often in
combination with other polymers like chitosan acetate.
Other Cellulose Ethers
Cellulose Acetate for Membrane
Systems
29-44.8% 156°C
Acetyl Content Range Softening Point
Determines properties and solubility behavior Can be manipulated using plasticizers
41.5°C
Phase Transition
For thermosensitive osmotic pump systems
Cellulose acetate is an insoluble cellulose derivative widely used in oral pharmaceutical
products. It is regarded as a nontoxic, nonirritant, and biodegradable material that is
heat-resistant and less hygroscopic. It's primarily used for forming semipermeable
coatings on tablets, especially in osmotic pump-type tablets and microparticles for
controlled release of drugs.
Ethylcellulose as a Coating Material
Film Formation
Excellent film-forming characteristics make it one of the most important coating
polymers in controlled release dosage forms
2 Water Insolubility
Ethylcellulose membrane is not swellable, providing consistent barrier properties
Excipient Compatibility
Compatible with most plasticizers and pore-forming substances, allowing
adjustment of drug release rates
Aqueous Dispersions
Surelease and similar products offer environmental benefits by avoiding organic solvents
Ethylcellulose is a hydrophobic cellulose ether used extensively as a coating material, tablet
binder, and matrix former in microcapsules, microspheres, and controlled release dosage forms.
The degree of substitution of commercial ethylcellulose grades ranges from 2.25 to 2.81, with
higher substitution resulting in more hydrophobic properties.
Polymethacrylates (Eudragit)
Acrylic resins such as polymethacrylates have excellent film-forming characteristics and are used for coating tablets, pellets,
capsules, and granules. Eudragit is a trade name of copolymers derived from esters of acrylic and methacrylic acids, whose
properties are determined by functional groups.
Different Eudragit grades offer various release profiles: gastrosoluble (E/NE), enteric (L/S), colon-targeted (FS), and extended-
release (RL/RS) types. This variety provides formulators with excellent options for controlled drug delivery in various
pharmaceutical applications.
Bioadhesive Polymers
Mechanism Hydration
Adhere to biological surfaces like Many polymers adhere upon
mucus, extending residence time 1 hydration at the mucus gel layer of
for drug absorption epithelial surfaces
Key Polymers Chemical Bonds
Carbomers, polyethylene oxides, Form ionic bonds, van der Waals
chitosan, alginate, and thiolated interactions, or hydrogen bonds
polymers with mucus
Bioadhesive controlled delivery systems are emerging as potential drug delivery systems due to their ability to prolong
gastrointestinal residence time, enhance contact between drug and absorbing surface, and improve bioavailability. The
force of attachment is related to the depth of interpenetration between polymers and mucous.
Carbomers and Polyethylene Oxide
Property Carbomers Polyethylene Oxide
Chemical Nature Cross-linked acrylic acid polymers Nonionic homopolymer of ethylene oxide
pH Sensitivity pH-dependent swelling pH-independent swelling
Swelling Capacity Up to 1000 times original volume Approximately twice that of HPMC
Bioadhesion Excellent at low pH (protonated state) Excellent across pH ranges
Commercial Names Carbopol, Carboxyvinyl Polymer Polyox
Carbomers and polyethylene oxide are two important bioadhesive polymers used in controlled release formulations. Carbomers form pH-dependent gels
that remain intact during swelling, while polyethylene oxide shows pH-independent swelling. Both can be used to achieve zero-order release kinetics
through careful formulation design.