Pharmaceutical Solid-State Chemistry Lecture Notes PDF

Summary

These notes provide an overview of pharmaceutical solid-state chemistry, focusing on methods to improve drug solubility including complexation and chemical modification. The lecture covers various types of non-aqueous solvents, their applications, and their selection criteria in formulation development.

Full Transcript

# Complexation - Poorly soluble drug + soluble material = soluble intermolecular complex - Most complexes are macromolecular = inactive (unable to cross lipid membranes) - complex formation is easily reversible - Many complexs are not water-soluble (prolonged release of the drug) - E.g.1 Polyvinylp...

# Complexation - Poorly soluble drug + soluble material = soluble intermolecular complex - Most complexes are macromolecular = inactive (unable to cross lipid membranes) - complex formation is easily reversible - Many complexs are not water-soluble (prolonged release of the drug) - E.g.1 Polyvinylpyrrolidone (PVP) + Iodine = Improved aqueous solubility of Iodine - E.g. 2. Cyclodextrins - a series of glucopyranose units that form cyclical structures resembling hollow cylinders (conical). - The inside surface is hydrophobic ($-CH_2$), the outer part is hydrophilic (OH). - Poorly water-soluble drugs accommodate inside > freely water-soluble inclusion complex. # Chemical Modification - Poorly soluble acids and bases -> a salt form to increase aqueous solubility. - E.g. The synthesis of the sodium phosphate salts of hydrocortisone, prednisolone and betamethasone. # Nonaqueous Solutions - **Uses:** - Stability - Depot (Propionate and benzoate esters of testosterone and estradiol) - **Choice:** - Toxicity, irritancy and sensitizing - Flammability, cost, stability and compatibility with other excipients - Parenteral products the choice is limited even further. # Classification of Nonaqueous Solvents ## 1. Fixed Oils of vegetable origin - Non-volatile oils that consist mainly of fatty acid esters of glycerol - Almond oil (glycerides mainly of oleic acid) for oily phenol injections. - Castor oil: solvent in miconazole eye drops. - Olives oil, sesame oil, maize oil, cottonseed oil, soya oil and castor oil: parenteral - Oils externally (emulsion). Arachis oil / Methyl Salicylate Liniment. ## 2. Alcohols - Ethyl alcohol (external / cooling / salicylic acid lotion) - Industrial methylated spirit (IMS) - Isopropyl alcohol (diclophane / abuse / denaturation) ## 3. Polyhydric Alcohols - Glycols (toxic) - Propylene glycol: Diazepam Injection, Cotrimoxazole IV Infusion, Chloramphenicol Ear Drops, hydrocortisone ear drops - PEG 400: cosolvent with water (glycerol) / water-miscible ointment bases clotrimazole topical solution. ## 4. Dimethylsulphoxide (DMSO) - Highly polar - Aid the penetration of drugs through the skin - Mainly for veterinary drugs - Idoxuridine for application to human skin. ## 5. Ethyl ether - Not internal (therapeutic) - A cosolvent with alcohol some collodions - Extraction of crude drugs ## 6. Miscellaneous Solvents - Isopropyl myristate/isopropyl palmitate cosmetics - Xylene: ear drops / dissolve earwax

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