Optimization of nifedipine loaded gastroretentive microcapsules for biliary colic

Shaheen Sultana, Sushma Talegaonkar, Aseem Bhatnagar, Farhan J Ahmad, Gaurav Mittal

Abstract


The aim of this research work was to formulate and systematically evaluate in vitro performance of gastroretentive microcapsules of nifedipine for biliary colic. Cross‐linked reinforced alginate‐chitosan microcapsules were prepared by
ionotropic gelation method using calcium chloride (CaCl2) as a cross‐linking agent. The microcapsules were evaluated for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy, drug entrapment efficiency, in vitro drug release and in vitro bioadhesion studies. Results of preliminary trials indicated that the
polymer concentration, cross‐linking agent and chitosan had a noticeable effect on size and surface morphology. A Box‐Behnken design was employed to study the effect of independent variables, polymer concentration (X1), CaCl2 concentration (X2), chitosan (X3) and pH of encapsulation medium (X4) on dependent variables, drug entrapment efficiency and percentage drug
release respectively.The entrapment efficiency varied from 6.14 to 79.21% depending upon the independent variables.The release can be sustained for more than 7 hours for all batches. It was observed that polymer and cross‐linker concentration had a more significant effect on the dependent variables.Validation of optimization study, performed using 6 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (± SD) as ‐0.85 ± 4.39% and 2.83 ± 2.91% for drug entrapment and drug release. Optimization was done on the basis of maximum
entrapment (82.26%) which was predicted using 6% alginate, 8.11% CaCl2, 2% chitosan at a pH of 3.55 of encapsulation medium.The optimized formulation depicted a release of 57.17% at 7 hours. Point prediction tool of design expert software shows 101.91% and 96.82% validity of the predicted model for drug entrapment and percent drug release. The release follow Higuchi kinetics followed by non‐fickian diffusion process. In vitro wash off test showed 71% bioadhesion after 1 hour.


Full Text:

PDF

References


Shaffer EA. Morphine and biliary pain revisited. Gut 2000;46:750‐1.

Rath SK Sarangi RR, Panda SK, Dash AK, Rath S, Nayak S.

Uv‐Spectrophotometric method for simultaneous estimation

Of drotaverine hydrochloride and aceclofenac In bulk and their

formulation. Int J Biol Pharm Res 2011;2:55‐9.

Craig A, Toouli J. Sphincter of oddi dysfunction: Is there a role for

medical therapy? Curr Gastroenterol Rep 2002;4:172‐6.

Griffiths AJ, Kennedy JF. Biotechnology of polysaccharides. In: Carbohydrates

chemistry. Kennedy JF, editor. New York, NY: Oxford University Press; 1988.

Higgs PG, Bael RC. A Reel‐chain model for the elasticity of bipolymer

gels, and its relationship to slip‐link treatment of entanglements, in

physical networks, Polymers and Gels. In: Burchard W, Ross SB, Murphy,

editors. New York, NY: Elsevier; 1990. p. 185‐94.

Clarks AH, Ross‐Murphy SB. Structural and mechanical properties of

biopolymer gels. Adv Polym Sci 1987;83:57‐192.

Ouwerx C, Velings CN, Mestdagh MM, Axelos MA. Physicochemical

properties and rheology of alginate gel beads formed with various

divalent cations. Polymer Gels Net 1998;6:393‐408.

Bajpai SK, Sharma S. Investigation of swelling/degradation behavior of

alginate beads cross linked with Ca2+ and Ba2+ ions. Reactive Functional

Polym 2004;59:129‐40.

Silva CM, Ribeiro AJ, Figueiredo M, Ferreira D, Veiga F. Microencapsulation

of Hemoglobin in Chitosan‐coated Alginate Microspheres Prepared by

Emulsification/Internal Gelation. AAPS J 2006;7:E903‐13.

Gombotz WR, Wee S. Protein Release from Alginate Matrices. Adv Drug

Deliv Rev 1998;31:267‐85.

Patil VB, Pokharkar VB. Preparation and evaluation of sustained release

nimesulide microspheres prepared from sodium alginate. Ind J Pharm

Sci 2001;63:15‐9.

Bodmeier R, Paeratakul O. Spherical agglomerates of water‐insoluble

drugs. J Pharm Sci 1989;78:964‐7.

Murata Y, Maeda T, Miyamoto E, Kawashima S. Preparation of

chitosan‐reinforced alginate gel beads‐effects of chitosan on gel matrix

erosion. Int J Pharm 1993;96:139‐45.

Polk A, Amsden B, Yao KD, Peng T, Goosen MF. Controlled release

of Albumin from chitosan‐alginate microcapsules. J Pharm Sci

;83:178‐85.

Takahashi T, Takayama K, Machida Y, Nagai T. Characteristics of polyion

complexes of chitosan with sodium alginate and sodium polyacrylate.

Int J Pharm 1990;61:35‐41.

Sezer AD, Akbuga J. Release characteristics of chitosan treated alginate

beads: Sustained release of a macromolecular drug from chitosan

treated alginate beads. J Microencapsul 1999;16:195‐203.

Hari PR, Candy T, Sharma CP. Chitosan/calcium‐alginate beads for oral

delivery of insulin. J Appl Polymer Sci 1996;59:1795‐801.

Polk AE, Scarratt AD, Gonzal A, Okhamafe AO, Goosen. Oral delivery

in aquaculture: Controlled release of proteins from chitosan‐alginate

microcapsules. Aquaculture Eng 1994;13:311‐23.

Anal AK, Stevens WF. Chtiosan‐Alginate multiplayer beads for controlled

release of ampicillin. Int J Pharm 2005;290:45‐54.

Patel JK, Bodar MS, Amin AF, Patel MM. Formulation and optimization

of mucoadhesive microspheres of metoclopramide. Ind J Pharm Sci

;66:300‐5.

Chaudary KR, Rao YS. Preparation and evaluation of mucoadhesive

microcapsules of Indomethacin. Ind J Pharm Sci 2003;65:49‐52.

Sriamornsak P, Kennedy RA. A novel gel formation method,

microstructure and mechanical properties of calcium polysaccharide

gel films. Int J Pharm 2006;323:72‐80.

Sriamornsak P, Nunthanid J. Calcium pectinate gel beads for controlled

release drug delivery: I. Preparation and invitro release studies. Int J

Pharm 1998;160:207‐12.

Sriamornsak P, Nunthanid J. Calcium pectinate gel beads for controlled

release drug delivery: II. Efect of formulation and processing variables

on drug release. J Microencapsul 1998;16:303‐13.

Peniche C, Howland I, Carrillo O, Zaldivar C, Arguelles‐Monal W.

Formation and stability of shark liver oil loaded chitosan/calcium

algiante capsules. Food Hydrocolloid 2004;18:865‐71.

Gupta KC, Jabrail FH. Glutaraldehyde cross‐linked chitosan

microspheres for controlled release of centchroman, Carbohydr Res

;342:2244‐52.

Dakhara SL, Anajwala CC. Polyelectrolyte complex: A pharmaceutical

review. Syst Rev Pharm 2010;1:121‐7.

Rajinikanth PS, Sankar C, Mishra B. Sodium alginate microspheres of

metoprololtartarate for intranasal systemic delivery: Development and

evaluation. Drug Deliv 2003;10:21‐8.

Takka S, Acartürk F. Calcium alginate microparticles for oral

administration: I. Effect of sodium alginate type on drug release and

drug entrapment efficiency. J Microencapsul 1999;16:275‐90.

Mirghani A, Idkaidek NM, Salem MS, Najib NM. Formulation and

release behavior of diclofenac sodium in compritol 888 matrix beads

encapsulated in alginate. Drug DevInd Pharm 2000;26:791‐5.

Ostberg T, Lund ME, Graffner C. Calcium alginate matricesfor oral

multiple unit administration: IV. Release characteristics in different

media. Int J Pharm 1994;112:241‐8.

Bayomi MA. Aqueous preparation and evaluation of albumin‐chitosan

microspheres containing Indomethacin. Drug DevInd Pharm

;30:329‐39.

Sriamornsak P, Burapapadh K, Puttipipatkhacehorn S, Nunthanid J.

Effect of acidic medium on swelling and release behaviors of

Chitosan‐Reinforced calcium pectinate gel beads. Silpakorn U Sci

Technol J 2008;2:37‐44.

Pasparakis G, Bouropolous N. Swelling studies and in vitro release of

verapamil from calcium alginate and calcium alginate‐chitosan beads.

Int J Pharm 2006;323:34‐42.




DOI: http://dx.doi.org/10.22377/ajp.v6i4.218

Refbacks

  • There are currently no refbacks.