JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B.Pharmacy IV NOVEL DRUG DELIVERY SYSTEMS Previous Question Paper (July-2021 - R17)

The design of controlled release (CR) systems depends on the drug's ability to be released at a predictable rate and absorbed effectively. Key physicochemical properties include:

• Aqueous Solubility: Drugs with very low solubility are poor candidates as their release is dissolution-rate limited, while highly soluble drugs require complex matrix systems to prevent dose dumping.
• Partition Coefficient (Log P): This determines the drug's lipophilicity. An optimal Log P (typically 1–3) is required for effective membrane permeation.
• Molecular Weight: Smaller molecules (typically < 500 Da) generally show better diffusion through polymer matrices and biological membranes.
• pKa and Ionization: The degree of ionization at physiological pH affects diffusion; only the unionized form typically crosses lipid membranes.
• Stability: The drug must be stable in the gastrointestinal environment and within the delivery system during storage.

Key biological properties include:

• Absorption: The drug must have a wide absorption window; drugs absorbed only in the upper GI tract are unsuitable for sustained release.
• Half-life (t1/2): Drugs with short half-lives (0.5–8 hours) are ideal candidates for CR to reduce dosing frequency.
• Therapeutic Index: Drugs with a narrow therapeutic index are preferred candidates for CR to avoid toxic peaks and sub-therapeutic troughs.
• Metabolism: Significant first-pass metabolism may necessitate specific delivery strategies to bypass the liver.

Polymers are the backbone of controlled drug delivery systems, providing the structural framework to modulate drug release. Their advantages include:

• Versatility: Polymers can be tailored (via molecular weight or cross-linking) to provide zero-order, first-order, or pulsatile release profiles.
• Biocompatibility and Safety: Many synthetic (e.g., PLGA) and natural (e.g., Chitosan) polymers are non-toxic and biodegradable, minimizing adverse reactions.
• Protection: They shield sensitive drugs from enzymatic degradation or acidic pH in the stomach.
• Targeting: Functionalized polymers can facilitate site-specific delivery, such as mucoadhesion or pH-sensitive release in the colon.

Applications of polymers include:

• Matrix Systems: Drugs are dispersed in a polymer matrix (e.g., HPMC), where release is controlled by diffusion or matrix erosion.
• Reservoir Systems: A drug core is surrounded by a rate-controlling polymer membrane (e.g., Ethyl cellulose).
• Biodegradable Implants: Polymers like PLA/PGA are used for long-term parenteral delivery, where the device slowly degrades, releasing the drug over weeks or months.
• Hydrogels: Cross-linked hydrophilic polymers that swell in water, used for controlled delivery of proteins and peptides.