Purpose: The purpose of this study was to develop a topical suspension formulation of drugs with poor aqueous solubility and evaluate the product quality using particle size and content uniformity.
Methods: Aqueous gel based suspensions with known quantity of drug were formulated using various viscosity modifiers, gelling agents, surfactants and suspending agents. The excipient levels were modified and formulations were visually evaluated to determine re-suspension capability of the drug. The uneven particle size distribution could account for irregular suspension and cake formation. Therefore, the particle size of the drug was reduced by micronization process. Formulation with uniform micronized particles were prepared and evaluated for content uniformity, drying time and physical appearance. Each formulation was prepared with appropriate dispersion technique. The formulations were left to stir at various speeds (medium and high) for 8 days. Three samples each from top middle and bottom portion of the formulation were collected and analyzed for drug content by HPLC. The drying time test involved measuring the time it takes for a formulation (20µL) to dry off completely when spread on glass slide using a bird applicator.
Results: The physical testing of the formulation with uniform particle distribution gave improved uniform pourable suspension as compared to suspension with irregular particles that contributed to cake formation. In addition, increased propylene glycol, gelling agent, and addition of polysorbate 80 aided in re-suspension ability of the particles. Results from the content uniformity study indicated mixing for 2 hours at 600 rpm resulted in assay values of 100.5%, 98.0%, 97.9% from top, middle, and bottom, respectively. Drying time was improved from 4.3 minutes to 0.45 minutes with increase in ethanol content from 20% to 40%, respectively.
Conclusion: Topical suspension based formulations are necessary for poorly water-soluble drugs. Critical quality attributes for these suspension formulations include appearance, content uniformity, and drying time. In this study, we successfully developed a topical aqueous gel formulation that was uniform, dispersible, had appropriate particle size, and ideal drying time and aesthetics.
Gayathri Krishnan
– Principal Scientist, Tergus Pharma, Durham, North CarolinaGayathri Krishnan
– Principal Scientist, Tergus Pharma, Durham, North CarolinaMeera Patel
– Manager, Tergus Pharma, LLC, DurhamVijendra Nalamothu
– CEO, Tergus Pharma, LLC, Durham, North CarolinaVijendra Nalamothu
– CEO, Tergus Pharma, LLC, Durham, North CarolinaGayathri Krishnan
– Principal Scientist, Tergus Pharma, Durham, North Carolina282 Views