Drug incompatibility

• Drug Incompatibilities are problems which could occur as a result of interaction between two or more drugs or chemicals, including physical, chemical and therapeutic incompatibilities.
• Stability is the capability of a particular formulation to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications.
• Pre-market stability studies support the clinical trial where drug products are stored under different conditions for safety and efficacy evaluation.
• Epimerization is the formation of the pair of diasteriomers that differ only in the configuration about one carbon atom (epimers).
• Polymerization is a chemical reaction in which two or more molecules combine to form larger molecules that contain repeating structural units.
• Explosive mixtures can occur when a reducing agent (RA) and an oxidizing agent (OA) are combined, when sugar is combined with KMnO4, or when glycerin is combined with KMnO4.
• Cementation is the formation of a cake (Acacia + Bismuth salts) or gel (Acacia + Iron salts) due to the action of heat.
• Photolysis, also known as photodecomposition or degradation by light, manifests as a change in color.
• The rate of epimerization is dependent on pH and the presence of citrates and phosphate ions.
• Gelatinization is the formation of a gel (Acacia + Iron salts) due to the action of heat.
• Racemization is a process where one enantiomer is more physiologically active than the other and racemization easily takes place.
• Commercial stability is the continuous assurance on the post-approval batches for long-term stability monitoring on the drug product.
• Precipitant drug is a drug, chemical or food causing the interaction.
• Occurrence of a toxic manifestation within the patient is referred to as a toxic reaction.
• Purposes of stability studies include supporting the stability of the drug product used in clinical/non-clinical studies, establishing commercial expiry date, determining levels for certain specifications (API, preservatives, etc.) and setting the control limits for lot release.
• Undesirable pharmacological interactions between two or more ingredients that lead to additive or potentiated therapeutic effects may cause toxicity or death.
• Antagonistic or destruction of the effect is when the interaction results in sub-therapeutic or lack of effect.
• Minimizing side effects is achieved when Furosemide + Spironolactone decreases hypokalemic effect of Furosemide.
• Object drug is the drug affected by the interaction.
• Examples of therapeutic incompatibilities include:
• Potentiated therapeutic effects are observed when Amoxicillin + Clavulanic acid increases resistance against penicillinase.
• Examples of therapeutic activity loss due to pharmacological interactions include:
• ↓ therapeutic activity of pen G after giving tetracycline (bacteriostatic).
• Therapeutic incompatibilities are desirable pharmacological interactions between two or more ingredients that lead to potentiated therapeutic effects or minimize side effects.
• Chemical stability is manifested by the drug’s molecular structure and chemical change results in different drug molecules.
• Each active ingredient should retain its chemical integrity and labeled potency within specified limits.
• Physical stability refers to the properties of drugs and dosage forms that can be seen or tested by physical means such as appearance, palatability, uniformity, dissolution, and suspendability.
• Organoleptic testing involves the assessment of flavour, odour, appearance and mouthfeel of a product.
• Sterility or resistance to microbial growth is retained according to the specified requirements.
• The therapeutic effect remains unchanged.
• If the pH of Phenobarbital Na (Salt form) needs to be lowered, some of the salt form will be converted to neutral free acid form, resulting in precipitation.
• Insolubility of components can lead to physical incompatibility.
• Consult prescriber for any changes in the prescription to remedy insolubility of components.
• Examples of insoluble components include gum & alcohol, pectin & alcohol, resin & water, and oil & water.
• Solvent effects can affect the solubility of the drug.
• Examples of immiscible components include castor oil emulsion, glycerin & water, and alcohol & water.
• For oral or topical product, make suspension or emulsion, if possible, to remedy insolubility of components.
• Use of an appropriate solvent system can remedy insolubility of components.
• Immiscibility of components can lead to physical incompatibility.
• When water is added to an alcoholic solution of a drug that is poorly soluble in water or if alcohol is added to an aqueous solution of a drug that is poorly soluble in alcohol, precipitation can occur.