Untitled Quiz

Pharmaceutical Technology I - 3rd Stage

• Solvent used in pharmaceutical preparations and oral solutions
• Water is the most widely used solvent for pharmaceutical products due to lack of toxicity, physiological compatibility, and its ability to dissolve a wide range of materials
• Naturally occurring water contains dissolved inorganic salts (sodium, potassium, calcium, magnesium, and iron), chlorides, sulfates, bicarbonates, dissolved and undissolved organic matter, and microorganisms.

Types of Pharmaceutical Water

• Tap Water/Drinking Water/Potable Water: Contains less than 0.1% total solids; clear, colorless, odorless, and neutral or slightly acidic/alkaline; unsuitable for most pharmaceutical preparations due to potential chemical incompatibilities (precipitation, discoloration, effervescence). Used for washing, extracting crude vegetable drugs, and preparing some external use products; can be used economically for cleaning machinery.
• Purified Water, USP: Contains fewer solid impurities than tap water, with a maximum 0.001% residue; used for preparing aqueous dosage forms (except parenteral). Obtained through distillation, ion exchange, and reverse osmosis.
• Sterile Water for Injection, USP: Sterile, pyrogen-free, packaged in single units (less than 1 litre); used in injection preparation.
• Bacteriostatic Water for Injection, USP: Sterile/pyrogen-free water with antimicrobial agents (SWFI); used in multiple-dosing injections.

Distillation Method

• Discarding the First Portion of Distillate: Initial 10-20% discarded due to volatile substances commonly found in urban drinking water.
• Discarding the Last Portion of Water: Final 10% discarded because the remaining solid impurities can decompose into volatile substances, contaminating the distillate.

Ion Exchange Demineralizer

• Advantages over Distillation: Eliminates the need for heat, simpler equipment, minimal maintenance, and more mobile facility.
• Ion Exchange Equipment: Water is passed through columns containing cation and anion exchangers. Exchangers are water-insoluble synthetic polymers.
• Types of Resins:
  • Cation (Acid) Exchangers: replace cations (e.g., Na+) with hydrogen ions from the resin.
  • Anion (Base) Exchangers: remove anions (e.g., Cl−) from the solution. Water purified in this manner is referred to as demineralized or deionized water.

Reverse Osmosis

• A type of cross-flow membrane filtration
• Water flows from a more concentrated to a less concentrated solution
• Removes nearly all viruses, bacteria, pyrogens, and organic molecules; 90-99% of ions.
• Filtration levels: microfiltration (0.1-2 µm), ultrafiltration (0.01-0.1 µm), nanofiltration (0.001-0.01 µm), reverse osmosis (<0.001 µm)

Non-Aqueous Solvents

• Used in intramuscular injections for depot therapy. Factors affecting choice: toxicity, irritancy, flammability, cost, stability, and compatibility with other excipients.
• Alcohol, USP (Ethyl Alcohol, Ethanol): Primary solvent for many organic compounds. Used as an antimicrobial preservative (with other agents like parabens, benzoates, and sorbates); frequently used with other solvents like glycols and glycerin to reduce alcohol amount. FDA recommends limiting alcohol content in OTC oral products (0.5% for children under 6, 5% for children aged 6-12, 10% for those over 12 and adults)
• Rubbing Alcohol: Contains about 70% ethyl alcohol; volatile and flammable; rubefacient, germicide, skin cleanser; used for topical preparations.
• Isopropyl Rubbing Alcohol: 70% by volume isopropyl alcohol; rubefacient, skin cleanser for preparation of needles and syringes.
• Glycerin, USP (Glycerol): Clear syrupy liquid with sweet taste; miscible with water and alcohol; preservative qualities, often used as a stabilizer in internal preparations, and high concentrations in external preparations like phenol ear drops.
• Propylene Glycol, USP: Viscous liquid; miscible with water and alcohol; frequently substituted for glycerin.
• Fixed oils of vegetable origin: Nonvolatile oils (e.g., almond, olive, sesame, maize) suitable for parenteral use, some suitable for oral use as solvents for vitamins (A) and (D); fractionated coconut oil used for phenoxymethyl penicillin, which would hydrolyze rapidly in an aqueous solution; oils are frequently presented as emulsions.
• Dimethyl sulphoxide (DMSO): Highly polar compound thought to aid drug penetration through the skin.
• Ethyl ether: Used in extraction of crude drugs; often used as a cosolvent.

Formulation Additives in Solutions

• Buffers: Resist pH changes when acid or alkali is added; compatible with other excipients; low toxicity; examples: carbonates, citrates, gluconates, lactates, phosphates, and tartrates (borates can be used for external application but not for mucous membranes or abraded skin)
• Flavors and Perfumes: Enhance patient compliance; natural (fruit juices, aromatic oils) or synthetic (cheaper, more stable); available as extracts, alcoholic/aqueous solutions, syrups, or powders.

Oral Solutions

• Antioxidant: Prevents oxidation of substances (most common: ascorbic acid).
• Isotonicity Modifiers: Solutions made iso-osmotic with tissue fluid to avoid pain and irritation.
• Preservatives: Prevent microbial contamination and maintain product stability. Types: water-soluble (benzyl alcohol, benzalkonium chloride) and water-insoluble (parabens, phenoxyethanol)

Preparation of solutions

• Most pharmaceutical solutions are unsaturated
• Strengths are usually expressed in percentages

Methods for Preparation of Solutions

• Methods: prepared by simple solution, chemical reaction, sterilization, and extraction; techniques to hasten dissolution: applying heat, reducing particle size, and using solubilizing agents, vigorous agitation

Oral Solutions and Their Systemic Effects

• Oral solutions, syrups, elixirs, spirits, and tinctures are prepared for specific effects.
• Formulating a pharmaceutical solution must consider: solubility and stability of each solute, potential chemical/physical interactions, and solubility of components in solvents (stated in USP-NF).

Dry Mixtures for Solution

• Many medicinal agents (particularly antibiotics) have poor stability in aqueous solutions.
• Usually, the components (except solvent) are prepared as a stable dry mixture; the solvent is added as needed

Oral Rehydration Solutions (ORS)

• Designed for rapid fluid loss and electrolyte replacement to avoid serious dehydration; should not be mixed with other electrolyte-containing liquids

Magnesium Citrate Oral Solution

• Effervescent liquid with sweet, acidulous taste and lemon flavor; prepared by chemical reaction of magnesium carbonate with citric acid; contains magnesium citrate; used as a saline cathartic to relieve occasional constipation.