Preparation and evaluation of mucoadhesive simvastatin microcapsules using orifice gelation technique

Trishna Bal, Padala Narasimha Murthy, Shubhranshu Sengupta

Abstract


Preparation and characterization of Simvastatin/ Hydroxy propyl beta cyclodextrin (HPBCD) (SV/HPBCD) binary systems by co-grinding technique and formulating the binary system in oral mucoadhesive microcapsules by using hydrophilic
sodium alginate (SA) and another plant seed mucilage dillenia (obtained from Dillenia indica, Family, Dilleniaceae) using orificegelation technique and systematically evaluating in vitro by using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffractometer (XRD). The microcapsules were smooth and elegant in appearance showed no visible cracks as confirmed by SEM; and extended drug release of 72.682% upto 12 hours in phosphate buffer of pH 6.8; showing particle size within the range of 371.5-457 μm, and less angle of repose,
Hausner’s ratio and Carr’s consolidation index; and showed encapsulation efficiency of 63.068 ± 0.002 to 99.083 ± 0.017%.Thein vitro release data of optimized batch of microcapsules were plotted in various kinetic equations to understand the mechanisms and kinetics of drug release, which followed zero order kinetics and value of “n,” is calculated to be 0.505 and drug release was
diffusion controlled.The in vivo antihyperlipidemic activity of formulations in mice was carried out developing hyperlipidemia in mice and then administering the optimized formulations orally, and the formulation showed promising results.


Full Text:

PDF

References


Patil SB, Sawant KK. Development, optimization and in vitro evaluation

of alginate mucoadhesive microspheres of Carvedilol for nasal delivery.

J Microencapsul 2009;26:432-43.

Robinson JR, Vincent HL. Control drug release, fundamental and

applications. Mercel Dekker series Newyork, 1987; p. 44-50.

Vyas A, Saraf S, Saraf S. Cyclodextrin based novel drug delivery systems. J Incl Phenom Macrocycl Chem 2008;62:23-42.

Cheng H, Sutton SC, Pipikin JD, Zentner GM, Rogers JD, Schwartz I, et al.Evaluation of sustained /controlled release dosage forms of 3-hydroxy-

-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor in dogs

and humans. Pharm Res 1993;10:1683-7.

McClelland CA, Stubbs RJ, Fix JA, Pogany SA, Zentner GM. Enhancement

of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase

inhibitor efficacy through administration of a controlled-poroisity

osmotic pump dosage form. Pharm Res 1991;8:873-6.

Ambike AA, Mahadik KR, Paradhar A. Spray-dried amorphous solid

dispersions of simvastatin a low Tg drug: In vitro and In vivo evaluations.

Pharm Res 2005:990-8.

Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development of self emulsif ying drug delivery systems (SMEDDS) for oral

bioavailability enhancement of Simvastatin in beagle dogs. Int J Pharm

;274:65-73.

Martindale JE. The extra pharmacopoeia. Great Britain: The

Pharmaceutical Press; p. 250.

Zarghi A, Foroutan SM, Shafaati A, Khoddam A. Quantification

of carvedilol in human plasma by liquid chromatography using

fluorescence detection: Application in Pharmacokinetic studies. J Pharm

Biomed Anal 2007;44:250-3.

Jun SW, Kim MS, Kim JS, Park HJ, Lee S, Woo JS, et al. Preparation and

Characterization of simvastatin/hydroxypropyl-b-cyclodextrin inclusion

complex using supercritical antisolvent (SAS) process. Eur J Pharm

Biopharm 2007;66:413-21.

United States Pharmacopoeia, XXII and NF XVII. Vol 2. Rockville, MD:

USP Convention; 1990. p. 793.

Salsa T, Veiga F, Pina Me. Oral controlled release dosage forms. J.

Cellulose Ether polymers in hydrophilic matrices. Drug Dev Ind Pharm

;25:929-38.

Deasy PB. Microencapsulation and related processes. United States:

Mercel Dekker; 1984. p. 234-7.

Sharma HK, Sarangi B, Pradhan SP. Preparation and in vitro evaluation

of mucoadhesive microbeads containing Timolol maleate using

mucoadhesive substances of Dillenia indica L. Arch Pharm Sci Res

;1:181-8.

Bal T, Murthy PN. Studies of drug polymer interactions of Simvastatin

with various polymers. Int J Pharm Sci Res 2012;3:561-3.

Shankar NB, Kumar NU, Balakrishna PK, Kumar RP. Design and evaluation

of controlled release bhara gum microcapsules of famotidine for oral

use. Res J Pharm Technol 2008;1:433-6.

Higuchi T, Connors KA. Phase solubility Techniques. Adv Anal Chem

Instrum 1965;4:117-212.

Chowdary KP, Rao YS. Design and in vitro evaluation of mucoadhesive

microcapsules of Glipizide for oral controlled release. A technical note.

AAPS Pharm Sci Tech 2003;4:1-6.

Hirlekar R, Kadam V. Preparation and characterization of inclusion

complexes of Carvedilol with methyl-b-cyclodextrin. J.Incl Phenom

Macrocyclo Chem 2009;63:219-24.

Ranjha NM, khan H, Nazeem S. Encapsulation and characterization of

controlled release flubiprofen loaded microspheres using beeswax as

an encapsulating agent. J Mater Sci Mater Med 2010;21:1621-30.

Dhaliwal S, Jain S, Singh HP, Tiwary AK. Mucoadhesive microspheres

of gastrointestinal delivery of Acyclovir: In vitro and in vivo evaluation.

AAPS Pharm Sci Tech 2008;10:322-30.

Patil DA, Patil GB, Deshmukh PK, Belgamwar VS, Farsule RA. Chitosan

Coated Mucoadhesive multiparticulate drug delivery system for

Glicazide. Asian J Pharm Clin Res 2009;2:62-7.

Carl RL. Evaluating flow properties of solids. Chem Engg 1965;72:163-8.

Gupta A, Garg S, Roop KK. Measurement of bioadhesive strength of

mucoadhesive buccal tablets: Design of an in vitro assembly. Indian

drugs 1992;4:152-5.

Nampurath GK, Mathew SP, Khanna V, Zachariah RT, Kanji S,

Chamallamudi MR. Assesment of hypolipidemic activity of three

thiazolidine-4-ones in mice given high fat diet and fructose. Chem Biol

Interact 2008;171:363-8.

Devi R, Sharma DK. Hypolipidemic effects of different extracts of

Clerodendron colebrookianum Walp in normal and high fat diet-fed rats.

J Ethnopharmacol 2004;90:63-8.

Thelen KM, Rentsch KM, Gutteck U, Heverin M, Oliv M, Anderson U,

et al. Brain Cholesterol synthesis in mice is affected by high dose of

simvastatin but not of pravastatin. J Pharmacol Exp Ther 2006;2:1146-52.

Lichtman Ah, Clinton SK, Liyama K, Lonnelly PW, Libby P, Cybulsky MZ.

Hyperlipidemia and atherosclerotic lesion development in LDL receptor-

deficient mice fed defined semipurified diets with and without cholate.

Arterioscler Thromb Vasc Biol 2011;11:1938-44.

Rayalakshmi G, Reddy AR, Rajesham VV. A comparative

antihyperlipidemic activity of atorvastatin with simvastatin

in rats. Internet J Pharmacol 2009;6, diakses tanggall 13 April

Available from: www.ispub.com:80/journal/the-internet-

journal- of-pharmacology/volume-6-number-2/a-comparative-

antihyperlipidemic-activity-of-atorvastatin-with-simvastatin-in rats.

html. [Last accessed on 2012 Mar 19].

Dhawan S, Singla AK, Sinha VR. Evaluation of mucoadhesive properties

of chitosan microspheres prepared by different methods. AAPS

PharmSciTech 2004;5:1-7.

Bal T, Murthy PN, Pandey A. Evaluation of mucoadhesive carvedilol

microcapsules prepared using orifice gelation technique. J Pharm Res

;5:519-25.

Zhang Y, Zhang J, Jiang T, Wang S. Inclusion of poorely water soluble

drug Simvastatin in mesocellular foam nanoparticles: Drug loading and

release properties. Int J Pharm 2011;410:118-24.

Souza MA, Conceicao MM, Silva MC, Soledade LE, Souza AG. Thermal

and kinetic study of Statins-Simvastatin and Lovastatin. J Therm Anal

Calorim 2007;3:859-63.

Shewale BD, Sapkal NP, Ravi NA, Gaikwad NJ, Fursule A. Effects of

hydroxypropyl beta cyclodextrin on the solubility of Carvedilol. Indian

J Pharm Sci 2008;225-7.

Magnusdottir A, Masson M, Loftsson T. Cyclodextrins. J Incl Phenom

Macrocycl Chem 2002;44:213-8.

Esclusa-Diaz M, Torres-Labandeira J, Katta M, Vila-Jato J. Inclusion

complexes of Glibenclamide with 2-hydroxypropylbeta cyclodextrin

in solution and solid state. Eur J Pharm Sci 1994;1:291-6.

Bandi N, Wei W, Roberts CB, Kotra LP, Kompella UB. Preparation of

Budesonide and Indomethacin-hydroxypropyl-b-cyclodextrin (HPBCD)

complexes using a single step organic-solvent-free supercritical fluid

process. Eur J Pharm Sci 2004;23:159-68.




DOI: http://dx.doi.org/10.22377/ajp.v6i1.76

Refbacks

  • There are currently no refbacks.