(M1330-06-34) Significance of Drug Excipient Compatibility Studies in Topical Drug Product Development

Purpose: Excipients are the substances other than API, which are pharmacologically inert. Although defined pharmacologically inert, excipients are thought as true enablers of drug product performance. The word excipient originates from the Latin excipere, which means to receive, hence the excipient receives the drug substance. Excipients play a major role in drug product development process, in formulating a specific dosage form and their administration. Depending on the dosage form and its intended function, excipients with different functionalities such as penetration enhancers, antioxidants, preservatives, viscosity enhancers are selected to meet final drug product delivery requirements This poster concentrates on excipient screening process for various topical dosage forms such as creams, lotions, gels, and ointments using specific case studies including study design, analysis, and results. Drug Excipient Compatibility study is a very useful and supportive tool in pre-formulation studies. This process is used to understand the physical and chemical interactions of Drug substance with excipients that could potentially go into the formulation. The study is used to assess the behavior of API with various inactive ingredients and how they affect the formulation, the degradation profile, and the product behavior over time and at different stressed conditions. Drug excipient compatibility studies can simulate the accelerated drug stability testing and help understand the drug substance stability when combined with individual excipients, thus helping the product owner analyze the risk factors and other implications at a very early stage in the product development process.

Methods: This study includes a stability setup of drug substance and excipient combinations. The study can be performed with Excipient at IID limits in combination with drug substance or using 1:1 mixture of DS: Excipient as a worst-case representation of the interactions. A preparation of active drug substance along with a selected solvent for the study will be made to know the drug substance interactions in the solvent. Binary or Tertiary mixtures of active drug substance stock solution and individual excipients are weighed into scintillation vials. During generic product development, reverse engineering data shall be used to set the composition(%w/w) of individual excipient.

Results: Whole vial analysis is performed with desired dilutions to achieve HPLC method nominal concentration for analytical feasibility. Whole vial analysis is critical for the analysis as all excipients may not solubilize the DS as a uniform mixture to be able to accurately analyze the mixtures by HPLC. The samples are then analyzed using early phase HPLC method to understand the recovery and degradation profile of drug substance. This study results will not only provide information on which excipient is generating high impurities but also give us an insight on which excipient can help in stabilizing the product by mitigating degradation of the Drug Substance. Each time point analysis can take up to 4days to a week depending on sample size, extraction, and analysis time.

Conclusion: Topical product development is a growing sector in pharmaceutical industry due to the demand for treating chronic conditions such as eczema, Psoriasis, skin cancers and other muscular-joint ailments. When developing these topical products, all the chemistry and process variables must be adequately controlled and validated at very early stages of product development to avoid complications during batch scaling up. Every excipient that goes into the formulation must be carefully assessed for safety, efficacy, quality and how they impact overall product, product costs and stability. Choosing a wrong excipient can have negative outcomes on the product performance and compromises the quality. Although this is a time consuming and meticulous process, this one-time study during the early product development can help the formulators to a great extent to come up with ideal excipients for desired dosage form before even making initial prototypes thus saving time and manufacturing expenses.