Nanocrystals for improved topical delivery of medium soluble drug: A case study of acyclovir

Acyclovir is "difficult-to-deliver" topically owing to low lipophilicity and high melting point. The aim of the present study was to develop nanocrystal-based formulations of acyclovir for improved topical delivery. Nanosuspension was optimized with sodium lauryl sulphate and hydroxypropyl cellulose-LF as stabilizers using high speed homogenizer followed by wet media milling. Nanosuspension was characterized by optical microscopy, differential scanning calorimetry, powder-X ray diffraction, dynamic light scattering. Acyclovir nanocrystals were crystalline in nature and exhibited mean particle size of 400–500 nm. Saturation solubility of nanocrystals was improved 1.6-fold over micronized acyclovir. Skin permeation and ex-vivo dermatokinetic studies of cream formulations were performed on pig ear skin at dose of 5% w/w using Franz diffusion cells. Skin permeation studies revealed non-detectable amount of acyclovir in the receptor compartment of Franz diffusion cell. Nanosuspension showed 2- and 2.3-folds drug penetration into the stratum corneum (SC) and viable layers (viable epidermis, dermis), respectively over microsuspension. Nanocream showed 1.6-fold drug penetration into the SC and viable layers over microcream. Further, nanosuspension and nanocream showed statistically significant improvement of 6.3-fold and 2.4-fold in penetration into the viable layers than Zovirax® cold sore cream. Thus, these nano-formulations are useful to improve topical delivery of acyclovir and can help in the treatment of herpes simplex virus infections.