Development and evaluation of a self-emulsifying drug delivery system of amphotericin B

Article Sidebar

PDF
Published: Aug 26, 2014
DOI: https://doi.org/10.22377/ajp.v6i2.64

Main Article Content

Arundhati Bhattacharyya
Meenakshi Bajpai

Abstract

Amphotericin B is a polyene antifungal antibiotic belonging to Class IV of Biopharmaceutics Classification System which is not absorbed from the gastrointestinal tract after oral administration. The aim of this research work was to develop a self-emulsifying drug delivery system (SEDDS) of amphotericin B and to evaluate the dissolution and permeability of amphotericin B from the formulation. The solubility of amphotericin B in various oils, surfactants and cosurfactants was determined.Various SEDDS formulations were prepared with varying amounts of oil, surfactant and co-surfactant. Evaluation parameters for formulation optimization were drug content, self-emulsification, droplet size analysis, and precipitation studies. In vitro dissolution was studied in comparison to the pure drug. Permeability was studied using non-everted intestinal sac
method. The optimized formulation consisted of glycerol mono-oleate (10%, w/w), tween 80 (36%, w/w), polyethylene glycol 400 (27%, w/w), and propylene glycol (27%, w/w) with a drug content of about 8 mg per ml. The self-emulsifying formulation showed 100% dissolution within 30 minutes whereas the pure drug exhibited a very poor rate of dissolution.In vitro intestinal permeability was studied by noneverted intestinal sac method using rat intestine. The self-emulsifying formulation showed 100% drug permeation within 30 minutes compared to negligible permeation from the drug suspension.
The study demonstrates that SEDDS approach may be useful for enhancement of dissolution and intestinal permeation of amphotericin B belonging to class IV of Biopharmaceutic Classification System.

Downloads

Download data is not yet available.

Article Details

How to Cite
Bhattacharyya, A., & Bajpai, M. (2014). Development and evaluation of a self-emulsifying drug delivery system of amphotericin B. Asian Journal of Pharmaceutics (AJP), 6(2). https://doi.org/10.22377/ajp.v6i2.64
Issue
Vol. 6 No. 2 (2012): Apr-June
Section
Articles

This is an Open Access article distributed under the terms of the Attribution-Noncommercial 4.0 International License [CC BY-NC 4.0], which requires that reusers give credit to the creator. It allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, for noncommercial purposes only.

References

Pouton CW. Lipid formulations for oral administration of drugs: Non-

emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery

systems. Eur J Pharm Sci 2000;11:S93-8.

Constantinides PP. Lipid microemulsions for improving drug dissolution

and oral absorption: Physical and biopharmaceutical aspects. Pharm

Res 1995;12:1561-72.

Kim HJ, Yoon KA, Hahn M, Park ES, Chi SC. Preparation and in vitro

evaluation of self-microemulsifying drug delivery systems containing

idebenone. Drug Dev Ind Pharm 2000;26:523-9.

Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm 2004;274:65-73.

Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying

drug delivery systems (SEDDS) with polyglycolysed glycerides for

improving in vitro dissolution and oral absorption of lipophilic drugs.

Int J Pharm 1994;106:15-23.

Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ,

Pouton CW. Self-emulsifying drug delivery systems: Formulation and

biopharmaceutic evaluation of an investigational lipophilic compound.

Pharm Res 1992;9:87-93.

Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug

delivery systems (SEDDS) of coenzyme Q10: Formulation development

and bioavailability assessment. Int J Pharm 2001;212:233-46.

Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS)

for improved oral delivery of lipophilic drugs. Biomed Pharmacother

;58:173-82.

Meyer RD. Current role of therapy with amphotericin B. Clin Infect Dis

;14(Suppl 1):S154-60.

Thakur CP, Pandey AK, Sinha GP, Roy S, Behbehani K, Olliaro P.

Comparison of three treatment regimens with liposomal amphotericin

b (Ambisome) for visceral leishmaniasis in India: A randomized dose

finding study. Trans R Soc Trop Med Hyg 1996;90:319-22.

Rajagopalan N, Chen SC, Chow W. A study of the inclusion complex of

amphotericin B with î§-cyclodextrin. Int J Pharm 1986;29:161-8.

Bajpai M, Verma KC. Studies on amphotericin B solid dispersions

prepared using blend of carriers. The Eastern Pharmacist 1981;24:187-8.

Dangi JS, Vyas SP, Dixit VK. Effect of various lipid-bile salt mixed micelles on the intestinal absorption of amphotericin B in rat. Drug Dev Ind

Pharm 1998;24:631-5.

Kayser O, Olbrich C, Yardley V, Kiderlen AF, Croft SL. Formulation of

amphotericin B as nanosuspension for oral administration. Int J Pharm

;254:73-5.

Santangelo R, Paderu P, Delmas G, Chen ZW, Mannino R, Zarif L, et al.

Efficacy of oral cochleate-amphptericin B in a mouse model of systemic

candidiasis. Antimicrob Agent Chemother 2000;44:2356-60.

Zarif L, Graybill JR, Perlin D, Najvar L, Bocanegra R, Mannino RJ. Antifungal activity of Amphotericin B cochleates against candida albicans infectionin a mouse model. Antimicrob Agent Chemother 2000;44:1463-9.

Risovic V, Sachs-Barrable K, Boyd M, Wasan KM. Potential mechanisms by which Peceol increases the gastrointestinal absorption of amphotericin

B. Drug Dev Ind Pharm 2004;30:767-74.

Wasan EK, Bartlett K, Gershkovich P, Sivak O, Banno B, Wong Z, et al.

Development and characterization of oral lipid-based amphotericin B

formulations with enhanced drug solubility, stability and antifungal

activity in rats infected with Aspergillus fumigatus or Candida albicans.

Int J Pharm 2009;372:76-84.

Gershkovich P, Wasan EK, Lin M, Sivak O, Leon CG, Clement JG, et al.

Pharmacokinetics and biodistribution of amphotericin B in rats

following oral administration in a novel lipid-based formulation.

J Antimicrob Chemother 2009;64:101-8.

Risovic V, Boyd M, Choo E, Wasan KM. Effects of lipid-based oral

formulations on plasma and tissue amphotericin B concentrations

and renal toxicity in male rats. Antimicrob Agent Chemother

;47:3339-42.

Würthwein G, Groll AH, Hempel G, Adler-Shohet FC, Lieberman JM,

Walsh TJ, et al. Population pharmacokinetics of amphotericin B

lipid complex in neonates. Antimicrob Agent Chemother 2005;

:5092-8.

Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX. Prediction of human

absorption of natural compounds by the non-everted rat intestinal sac

model. Eur J Med Chem 2006;41:605-10.

Yamsani SK, Gannu R, Devandla A, Yamsani VV, Palem CR, Ravula SK,

et al. Effect of silymarin and pomegranate pretreatment on intestinal

transport of buspirone across rat intestine. Acta Pharmaceutica Sciencia

;51:289-96.

Adams ML, Kwon GS. Relative aggregation state and hemolytic activity

of amphotericin B encapsulated by poly(ethylene oxide)-block-poly

(N-hexyI-I-aspartamide)acyl conjugate micelles: Effects of acyl chain

length. Biochim Biophys Acta 1980;599:280-93.

Johnson BM, Charman WN, Porter CJ. An in vitro examination of the

impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-

tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein

efflux and enterocyte-based metabolism in excised rat intestine. AAPS

PharmSci 2002;4:E40.

Zhang H, Yao M, Morrison RA, Chong S. Commonly used surfactant,

Tween 80, improves absorption of P-glycoprotein substrate, digoxin,

in rats. Arch Pharm Res 2003;26:768-72.