Pharmaceutical Solutions Lecture 2

Pharmaceutical Solutions (Lecture 2)

• Intended learning outcomes include describing solution preparation, differentiating methods for enhancing drug solubility, detailing solution stability aspects and possible incompatibilities, and defining various oral and topical liquid dosage forms.
• Solution preparation involves weighing, dissolving, adjusting pH, adjusting volume, and labeling/storing.
• Techniques for preparing solutions include dissolution, mixing, filtration, and packaging.
• Factors affecting drug solubility include molecular structure, crystal structure, particle size, pKa, and pH of the medium (drug as weak acid/base or salt).
• Methods for enhancing drug solubility include co-solvents, pH adjustment, cyclodextrins, and surfactants/micelles.
• pH adjustment is a common technique to increase drug solubility by either increasing ionization of weak acids or decreasing ionization of weak bases.
• Buffer solutions (e.g., citrate, acetate, phosphate, carbonate) are used to adjust pH.
• The chosen pH should not negatively affect drug or excipient stability.
• Cyclodextrins (CDs) are non-reducing cyclic glucose oligosaccharides, comprising variable numbers of glucose residues. Alpha, beta, and gamma CDs consist of 6, 7, and 8 d-glucopyranosyl units, respectively, and are visualized as a hollow truncated cone.
• The cavity of cyclodextrins is hydrophobic, while the exterior is hydrophilic, enabling non-polar drugs to be embedded and dispersed in water.
• Solution stability involves maintaining physical, chemical, microbiological, therapeutic, and toxicological properties from manufacturing to use.
• Factors affecting physical stability include sorption of drug to containers, extraction of materials into liquid, shedding of particles, drug precipitation or degradation.
• Factors affecting chemical stability include temperature, light, humidity, oxygen, solvent composition, ionic strength, pH, and excipient compatibility; hydrolysis, oxidation, decarboxylation, epimerization, and polymerization are examples of chemical reactions.
• Incompatibilities can arise from excipient degradation (interaction with other excipients or drugs) or from interactions between preservatives (p-hydroxybenzoate) and other components (sorbitol). Drug degradation is also a type of incompatibility.
• Sodium metabisulphite, used as an antioxidant in epinephrine (adrenaline) injections, can react with epinephrine for significant degradation.
• Microbial stability is crucial for sterile products and solutions for injection/use or in multidose solutions; use of preservatives is critical to avoid growth.
• Quality control includes assessing appearance (clarity, no particulates), pH, assay (drug concentration), sterility, and stability (over shelf-life).
• Solutions can be classified by administration route: oral, oral cavity, topical, otic, nasal, pulmonary, rectal, vaginal, ocular, and parenteral.
• Regulatory framework for liquid dosage form solutions considers FDA, EMA, guidelines, and manufacturing, packaging, labeling requirements.
• Pharmacopoeial standards offer quality, purity, and performance of solution dosage forms.
• Good Manufacturing Practices (GMP) ensure production quality, consistency, and safety, covering facilities, equipment, personnel, and documentation.