Novel Drug Delivery Systems and Formulation Stability
~1 min read
Lesson 3 of 9
Notes
Lipid-Based Drug Delivery Systems
Lipid-based formulations improve oral bioavailability of hydrophobic BCS Class II and IV drugs. Systems include: (1) Self-emulsifying drug delivery systems (SEDDS) — oil/surfactant/co-surfactant mixtures that spontaneously emulsify in GI fluids, dispersing drug in fine droplets for absorption (e.g. cyclosporin, saquinavir); (2) Liposomes — phospholipid bilayer vesicles encapsulating hydrophilic (aqueous core) or hydrophobic (bilayer membrane) drugs; used to reduce toxicity (liposomal doxorubicin reduces cardiotoxicity), improve targeting; (3) Solid lipid nanoparticles (SLN) — solid lipid matrix with drug dispersed within; more stable than emulsions.
Nanoparticle Drug Delivery
Nanoparticles (10-1000 nm) improve drug delivery through the enhanced permeability and retention (EPR) effect in tumours, enabling passive targeting of cancers. Active targeting uses ligands (antibodies, peptides) on nanoparticle surface to bind specific receptors on target cells. Polymer-based nanoparticles (PLGA — poly-lactic-co-glycolic acid) are biodegradable and widely used. mRNA vaccines (COVID-19 vaccines) use lipid nanoparticles (LNPs) to protect mRNA from degradation and deliver it intracellularly to be translated into the spike protein antigen.
Formulation Stability
Drug stability is affected by hydrolysis (main degradation pathway for esters and amides), oxidation, photodegradation, and microbial contamination. The Arrhenius equation predicts the temperature dependence of reaction rates; accelerated stability testing (40°C/75% RH for 6 months) predicts shelf-life at 25°C. Strategies to improve stability: pH optimisation (maximum stability at drug-specific pH), antioxidants (sodium metabisulfite, BHA), nitrogen atmosphere, light-protected amber vials, lyophilisation (freeze-drying for reconstitutable IV preparations, e.g. vancomycin), cold chain for biologics (2-8°C for vaccines and protein therapeutics).