Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bioavailability

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Mangesh Ramesh Bhalekar
Prashant Girish Upadhaya
Satish Reddy
Sanjay J. Kshirsagar
Ashwini Raghvendra Madgulkar


Acyclovir, an antiviral drug used against herpes simplex virus and varicella zoster virus. The dose ranges between 200
and 800 mg and the oral bioavailability is 10‑20%, which decreases as the dose is increased. The aim of this research
work was to formulate and characterize nanosuspensions of acyclovir with an intention to increase the oral bioavailability.
Nanosuspensions were prepared by the precipitation-ultra sonication method and the effects of important process parameters i.e., precipitation temperature, stirring speed, end point temperature of probe sonicator, energy input and sonication time were investigated systematically, the optimal nanosuspension (particle size 274 nm) was obtained at values of 4°C, 10,000 rpm, 30°C, 600 Watt and 20 min, respectively. The nanosuspension was lyophilized using different matrix formers and sucrose (100% w/w to drug) was found to prevent agglomeration and particle size upon reconstitution was found to be 353 nm. The lyophilized nanocrystals appeared flaky in scanning electron microscopy images, the X‑ray powder diffraction and differential scanning calorimetry analysis showed the nanoparticles to be in the crystalline state. Ex vivo permeation study for calculating absorption rate and in vivo bioavailability area under the curve both showed three‑fold increase over marketed suspension.
Key words: Differential scanning calorimetry, ex vivo chicken intestine study, precipitation-ultra sonication, probe sonicator, scanning electron microscopy, X‑ray powder diffraction


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Bhalekar, M. R., Upadhaya, P. G., Reddy, S., Kshirsagar, S. J., & Madgulkar, A. R. (2014). Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bioavailability. Asian Journal of Pharmaceutics (AJP), 8(2).


Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising

drug delivery strategy. J Pharm Pharmacol 2004;56:827‑40.

Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug

formulations in therapy. Rationale for development and what we can

expect for the future. Adv Drug Deliv Rev 2001;47:3‑19.

Liversidge GG, Cundy KC, Bishop J, Czekai D. Surface modified drug

nanoparticles. US Patent No. 5145684; 1991.

Muller RH, Becker R, Kruss B, Peters K. Pharmaceutical nanosuspensions

for medicament administration as system of increased saturation

solubility and rate of solution, US Patent No. 5858410; 1998.

Chen Y, Liu J, Yang X, Zhao X, Xu H. Oleanolic acid nanosuspensions:

Preparation, in‑vitro characterization and enhanced hepatoprotective

effect. J Pharm Pharmacol 2005;57:259‑64.

Xia D, Quan P, Piao H, Sun S, Yin Y, et al. Preparation of stable

nitrendipine nanosuspensions using the precipitation‑ultrasonication

method for enhancement of dissolution and oral bioavailability. Eur J

Pharm Sci 2010;40:325‑34.

Agnihotri SM, Vavia PR. Diclofenac‑loaded biopolymeric nanosuspensions

for ophthalmic application. Nanomedicine 2009;5:90‑5.

Dixit P, Jain DK, Dumbwani J. Standardization of an ex vivo method for

determination of intestinal permeability of drugs using everted rat

intestine apparatus. J Pharmacol Toxicol Methods 2012;65:13‑7.

Technical Brochure, BASF Corporation. Available from: http://www.

pharma‑ [Last accessed on 2012 Aug 24].

Tao Y, Lu Y, Sun Y, Gu B, Lu W, Pan J. Development of mucoadhesive

microspheres of acyclovir with enhanced bioavailability. Int J Pharm


Boulieu R, Gallant C, Silberstein N. Determination of acyclovir in human

plasma by high‑performance liquid chromatography. J Chromatogr B

Biomed Sci Appl 1997;693:233‑6.

Product manual of probe sonicator VCX750. Available from: http://www.‑vibra.htm [Last accessed on 2012 Mar 23].

Hany SM. Preparation of hydrocortisone nanosuspension through a

bottom‑up nanoprecipitation technique using microfluidic reactors.

Int J Pharm 2009;375:107‑13.

Van Eerdenbrugh B, Van den Mooter G, Augustijns P. Top‑down production of drug nanocrystals: Nanosuspension stabilization, miniaturization and

transformation into solid products. Int J Pharm 2008;364:64‑75.

Kesisoglou F, Panmai S, Wu Y. Nanosizing-Oral formulation development

and biopharmaceutical evaluation. Adv Drug Deliv Rev 2007;59:631‑44.

Chingunpituk J. Nanosuspension technology for drug delivery. Walailak

J Sci Technol 2007;4:139‑53.