Nanosuspension coated multiparticulates for controlled delivery of albendazole

Abstract

Objective

Improving solubility and bioavailability of albendazole (ALB).

Significance

ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%.

Methods

ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 3² factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000–3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics.

Results

Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential −16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC_0-10h was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.

Keywords:

• Coating
• solubility
• antisolvent precipitation
• anthelmintic
• nanosuspension

Acknowledgements

The authors are thankful to Dr. Ashwini Madgulkar, Principal, AISSMS College of Pharmacy, Pune for her support and Vasantha Kumar Shetty, Head – Process technology support, ACG Pharma Technologies Pvt. Ltd. Shirwal, Maharashtra, India for providing facilities of fluid bed processor.

Disclosure statement

The authors’ report no declaration of interest, financial or otherwise regarding this project.