Improvement of Palatability for Oral oil Based Liquid Formulation

Abstract

Pharmaceutical industry today faces a significant problem in the formulation of diverse chemically complex drug molecules which are either BCS class II or IV drug candidates. Innumerable formulation strategies exist in design and delivery of such drug molecules. The drug molecule belongs to BCS class II and is lipophilic in nature. Numerous lipidbased formulation strategies exist to deliver lipophilic drug candidates. The aim of the project was to develop oral oil-based liquid formulation which is highly palatable, taking into consideration the fraction of or complete presence of oil. The oil used was combination of Medium chain (MCTs) and long chain triglyceride(LCTs). MCTs have the advantage of easy digestion and LCTs have the ability to bypass systemic circulation by getting absorbed through lymphatic system. Oral administration is the most preferred and widely accepted and targeted approach to deliver drugs. This is due to high patient compliance prevailing in oral formulations. The need for developing oral liquids is that it is more patient compliant in both pediatric and geriatric population as compared to oral solid formulation. The first formulation strategy was to develop a carrier technology for lipophilic drug molecules and thus objective was to taste mask and make palatable complete oil solutions. Highly taste masked and palatable complete oil solutions have the benefit of ease of manufacture, low cost and patient compliance. To taste mask oils various sweeteners and flavourants were utilized in different concentrations. The method of preparation was mixing under stirrer.The second formulation strategy was to develop an oil-in-water emulsion. Here two methods were investigated, one was development of microemulsions and second was development of nanoemulsions and taste masking them both. In microemulsion oil phase was same, mixture of MCT and LCT and in nanoemulsion only MCT was used. Surfactants and co-solvents were used in developing both microemulsions and nanoemulsions. Surfactants were non-ionic surfactants like Tweens, Poloxamers, Cremophors. Co-solvents were Propylene glycol, Polyethylene glycols and Transcutol. Microemulsions were prepared by simple high speed stirring. Preparation of nanoemulsions involved a two-step process were in, first step involved formation of crude emulsions by simple mixing and then using high energy technique which is probe sonication for creating nanoemulsions. Both microemulsion and nanoemulsion would be taste masked and then compared with taste masked oil solutions. After taste masking microemulsions and comparing it with taste masked complete oil solutions it was found that microemulsions needed less amount of flavourants and sweeteners to taste mask it, as compared to complete oil solutions. Complete oil solutions employed high concentration of flavourants which are GRAS listed, but still they need to be evaluated for safety and toxicity. All the formulation strategies were effectively taste masked and improved for their palatability.