(T1230-01-01) Developing a Stable Model Formulation to be Used as a Platform Technology for BCS Class II and IV Hydrophobic Molecules with Log P >3 while Using an Aprotic Solvent System as a Solubilizer and Carrier

Purpose: The purpose of this study is to develop a stable model topical formulation for BCS Class II and IV hydrophobic molecules with log P >3 while using an aprotic solvent system at a %w/w concentration of 20 and 40. The aprotic solvent system used is an excellent solubilizer and penetration enhancer. Considering BCS Class II and IV molecules have solubility and/ or permeation limitations, we wanted to harness these impeccable properties of the solvent to develop stable prototypes.

Methods: Upon thorough review of various excipients, a self-emulsifying wax Cetostearyl alcohol, an emollient Mineral oil and a self-emulsion GMS type II were selected to constitute the oil phase as the latter will also improve the solubilization lipophilic active pharmaceuticals. A combination of Low HLB and a High HLB surfactants such as Span 80 and Tween 80, both non-ionic stabilizes the emulsion having aprotic solvent systems at larger portions. Considering waxes and polymers almost always have a synergistic effect on building viscosity in conjunction with homopolymers. In view of the weak polymer- polymer interactions between the homopolymers and acrylamides which aid in improved consistency of the product by trapping the aprotic solvents in the form of droplets. cosolvents were incorporated to improve the solubility of both low range log P to mid-range log P molecules respectively.

Results: All batches were manufactured and were evaluated for accelerated stability conditions up to 3 months at 25°C/60%RH and 40°C/75%RH. They were evaluated for physical stability characteristics like appearance, microscopic analysis, pH and viscosity at given timepoints. The results are explained in the Table 1 below. Pictures of the final formulations are depicted in Figure 1.

Conclusion: Model formulations of the aprotic solvent system for BCS Class II and IV molecules were designed and established improved stability. Two each of Ointments, Emulgels and Gels were manufactured, one each at 20 and 40%w/w of the aprotic solvent. Albeit oleaginous ointments were designed, they were not physically stable over time. The other four are now considered lead prototypes and are undergoing a continued stability study at long term and accelerated storage conditions. Polymer based emulgels and hydrogels improved stability of the dosage forms by showing a gel trap evidence for binding aprotic solvent systems in between the polymer maltese crosses.


physical appearance of all prototypes


viscosity values of different prototypes at various stability timepoints


Short Term Physical Stability Data