Water Activity and Its Significance in Topical Dosage Forms.

Unique properties of thermodynamic activity of solvents in topical semisolids and its effects on in vitro product performance have not been fully understood. Mechanistic investigation was undertaken to demonstrate the significance of thermodynamic potential of solvents [water activity (aw) or solvent activity (as)] on in vitro performance of model topical formulations. Drug transport across synthetic membranes was found to decrease with decreasing water activity of formulations. Similarly, in vitro permeation of model permeant (caffeine) across porcine epidermis was found to decrease with decreasing water activity of formulations. Notably, relatively low water activity formulations (aw, 0.78) induced dehydration in porcine skin associated with significant structural changes like detachment of individual stratum corneum layers. Inclusion of hydrating agents (propylene glycol) in low water activity (aw, 0.78) formulations restored hydration levels and structural integrity of porcine skin. Most importantly, incremental inclusion of propylene glycol in low water activity formulations (aw, 0.78) enhanced in vitro permeation of model permeant (fluorescein sodium). Further investigation revealed that variability in processing conditions (high shear mixing during emulsification step) could modulate water activity in semisolid formulations despite their compositional sameness. In retrospect, water activity was found to be a critical quality attribute of topical semisolid products which impacts overall product performance and drug delivery.

Development of an Ointment Formulation Using Hot-Melt Extrusion Technology.

Ointments are generally prepared either by fusion or by levigation methods. The current study proposes the use of hot-melt extrusion (HME) processing for the preparation of a polyethylene glycol base ointment. Lidocaine was used as a model drug. A modified screw design was used in this process, and parameters such as feeding rate, barrel temperature, and screw speed were optimized to obtain a uniform product. The product characteristics were compared with an ointment of similar composition prepared by conventional fusion method. The rheological properties, drug release profile, and texture characteristics of the hot-melt extruded product were similar to the conventionally prepared product. This study demonstrates a novel application of the hot-melt extrusion process in the manufacturing of topical semi-solids.

Iontophoretic drug delivery for the treatment of scars.

Topical treatment of hypertrophic scars is challenging because of poor penetrability of drugs into the scar tissue. The objective of the study was to investigate the effectiveness of iontophoresis to deliver medicaments across the scar epidermis. Initially, biophysical studies were performed to investigate the differences between scar and normal skin epidermis obtained from cadaver. In case of scar skin epidermis, the transepidermal water loss was not significantly different from the normal skin epidermis, whereas the electrical resistivity was significantly higher. The passive permeation flux of sodium fluorescein was approximately one-third of that across the normal skin epidermis. Scanning electron microscopy studies revealed that the two membranes were alike except that the scar skin epidermis lacked follicles. Cathodal iontophoresis enhanced the delivery of sodium fluorescein across the scar skin epidermis by approximately 46 folds [51.90 ± 8.82 ng/(cm(2) h)]. However, the transport of sodium fluorescein across the scar skin epidermis was about an order of magnitude less than the normal skin epidermis. Overall, the studies suggest that iontophoresis could be utilized to overcome the barrier resistance of scar skin epidermis and treat the scar regionally.

Controlled-release injectable containing terbinafine/PLGA microspheres for onychomycosis treatment.

Controlled-release drug delivery systems based on biodegradable polymers have been extensively evaluated for use in localized drug delivery. In the present study, intralesionally injectable poly (lactide-co-glycolide) (PLGA) microspheres for controlled release of terbinafine hydrochloride (TH) was developed for treating fungal toe/finger nail infections. TH-PLGA microspheres were formulated using O/W emulsification and modified solvent extraction/evaporation technique. Microspheres were evaluated for particle size and size distribution, encapsulation efficiency, surface, and morphology. The in vitro drug release profile was studied in aqueous media as well as in 1% agar gel. Microspheres system was also evaluated in excised cadaver toe model, and extent of TH accumulation in nail bed, nail plate, and nail matrix was measured at different time points. Microspheres were found to provide consistent and sustained TH release. Intralesional administration of controlled-release microspheres can be a potential alternative mode of treating fungus-infected toe and/or finger nails.