Identification of critical formulation parameters affecting the in vitro release, permeation, and rheological properties of the acyclovir topical cream

• Published in: International journal of pharmaceutics Vol. 590; p. 119914
• Main Authors: Kamal, Nahid S., Krishnaiah, Yellela S.R., Xu, Xiaoming, Zidan, Ahmed S., Raney, Sameersingh, Cruz, Celia N., Ashraf, Muhammad
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 30.11.2020
• Subjects: Bioequivalence; In vitro permeation test (IVPT); In vitro release test (IVRT); Topical drug delivery; Topical formulation; In vitro release test (IVRT); Topical drug delivery; In vitro permeation test (IVPT); Topical formulation; Bioequivalence
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119914

Pareto charts of the standardized effects of various formulation variables on the (a) acyclovir release rate (mg/cm2 h0.5) and (b) acyclovir retained by the skin (µg/cm2). The chart shows estimate coefficients, t ratio and Prob > t values of the variables. The two vertical blue lines represent the significance limit of p = 0.05. Response surface (c and d) plots of the investigated responses, respectively. [Display omitted] To understand effects of formulation variables on the critical quality attributes (CQA) of acyclovir topical cream, this study investigated effects of propylene glycol (PG), poloxamer, and sodium lauryl sulfate (SLS) concentrations, acyclovir particle size, and formulation pH of the acyclovir cream. Fifteen formulations were prepared and characterized for rheological properties, particle size distribution, drug release and in vitro skin permeation. Drug distribution between various phases of the cream was determined. The concentration of soluble acyclovir in the aqueous phase was determined as a surrogate of the equilibrium with other acyclovir species in the cream. The interaction among effects of the formulation variables on the amount of acyclovir retained by skin was also evaluated. The results showed that PG significantly (p < 0.05) increased the yield stress, viscosity, drug concentration in the aqueous phase, and drug release. The PG and SLS significantly (p < 0.05) increased acyclovir retention by skin samples. Particle size of acyclovir inversely affected the drug release. This study revealed that the employed concentrations of PG and SLS and particle size of the dispersed acyclovir are critical formulation variables that should be carefully controlled when developing acyclovir topical creams with desired performance characteristics.