Preparation and characterization of nimesulide loaded poly (methyl methacrylate)/poly (ethylene oxide) blend microspheres: In vitro release studies

K. Sudhakar, K. Madhusudana Rao, B. Mallikarjuna, C. V. Prasad, M. C. S. Subha, K. Chowdoji Rao

Abstract


Poly (methyl methacrylate)/poly (ethylene oxide) (PMMA/PEO) blend microspheres were prepared by solvent evaporation technique using poly (vinyl alcohol) (PVA) as a stabilizer. Nimesulide, an arthritis drug was successfully
loaded into these microspheres. The effect of experimental variables such as ratio of ploy (methyl methacrylate) to poly (ethylene oxide) on nimesulide encapsulation efficiency, release rate, size, and morphology of the microspheres has been investigated. Nimesulide loaded microspheres were analyzed using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X‐ray diffraction (X‐RD), and scanning electron micrograph (SEM). FTIR spectroscopy was used to explain the blending of polymers. DSC and X‐RD techniques were used to investigate the crystalline nature of the drug after encapsulation. DSC and X‐RD results indicated a nonuniform dispersion of nimesulide in the PMMA/PEO blend matrix.SEMs indicated the formation of spherical microspheres with distinct size. Nimesulide was successfully encapsulated up to 85% in the polymeric matrices. In vitro dissolution experiments performed in pH 7.4 buffer medium indicated a controlled release of nimesulide from blend microspheres up to 12 h.


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Abu‐Izza K, Tambrallo L, Lu DR. In vivo evaluation of zidovudine

(AZT)‐loaded ethyl cellulose microspheres after oral administration in

beagle dogs. J Phar m Sci 1997;86:554‐559.

Galeone M, Nizzola L, Cacioli D, Mosie G.In Vitro demonstration of

delivery mechanism from sustained release pellets. Curr Ther Res

;29:217‐234.

O’Hagan DT, Palin K, Davis SS, Artursson P, Sjöholm I. Microparticles

as potentially orally active immunological adjuvants. Vaccine

;7:421‐424.

Herrmann J, Bodmier R. The effect of particle microstructure on the

somatostatin release from poly (lactide) microspheres prepared by a

W/O/W solvent evaporation method. J Control Release 1995;36:63‐71.

Sveinsson SJ, Kristmundsdottir T, Ingvarsottir K. The effect of tableting

on the release characteristics of naproxen and ibuprofen microcapsules.

Int J Pharm 1993;92:29‐34.

Bodmeier R, Chen H. Preparation of biodegradable poly (+/‐) lactide

microparticles using a spray drying technique. J Pharm Pharmacol

;40:754‐7.

Shah SS, Cha Y and Pitt CG Poly (glycolic acid‐co‐DL‐lactic acid):

diffusion or degrdation controlled drug delivery. J Control Release

;28:261–270.

Kulkarni AR, Soppimath KS, Aminabhavi TM, Dave AM, Mehta MH.

Glutaraldehyde crosslinked sodium alginate beads containing liquid

pesticide for soil application. J Control Release 2000;63:97‐105.

Goodell JA, Flick AB, Hebert JC, Howe JG. Preparation and release

characteristics of tobramycin‐impregnated poly methylmethacrylate

beads. Am J Hosp Surg 1986;43:1454‐146.

Calhoun JH, Mader JT. Antibiotic beads in the management of surgical

infections. Am J Surg 1989;157:443‐449.

Klem KW. Antibiotic bead chains. Clin Orthop Relat Res 1993;295:63‐76.

Josefsson G, Lindberg B, Wilander B. Systemic antibiotics and

gentamicin‐containing bone cement in the prophylaxis of postoperative

infections in total hip arthroplasty. Clin Orthop Relat Res 1981;159:194‐200.

del Real RP, Padilla S, Vallet‐Regí M. Gentamicin release from

hydroxyapatite/poly (ethyl methacrylate)/poly (methyl methacrylate)

composites. J Biomed Mater Res 2000;52:1‐7.

Hoff SF, Fitzgerald RH Jr, Kelly PJ. The depot administration of penicillin

G and gentamicin in acrylic bone cement. J Bone Joint Surg Am

;63:798‐804.

Wahlig H, Dingeldom E. Antibiotics and bone cements. Experimental

and clinical long‐term observations. Acta Orthop Scand 1980;51:49‐56.

Ranjha NM, Muddasari J, Akhtar N. Methyl Methacrylate‐co‐itaconic

acid (MMA‐co‐IA) hydrogels for controlled drug delivery. J Sol‐Gel Sci

Technol 2008;47:23‐30.

Issakatime, Virginia S, Estibaliz H. Nafcillin release from poly (acrylic

acid–co–methyl methacrylate) hydrogels. Poly Bull 2005;55:403‐409.

Sparnacci K, Laus M, Tondelli L, Magnani L, Bernardi C. Core–shell

microspheres by dispersion polymerization as drug delivery systems.

Macromol Chem Phys 2002;203:1364‐1369.

Babu VR, Sairam M, Hosamani KM, Aminabhavi TM. Development

of 5‐fluorouracil loaded poly (acrylamide‐co‐methylmethacrylate)

novel core‐shell microspheres: In vitro release studies. Int J Pharm

;325:55‐62.

Lakshminarayana Reddy C, Yerriswamy B, Prasad VC, Subha MC, Rao CK.

Control release of chlorpheniramine maleate through IPN beads of sodium

alginate‐g‐methyl methacrylate. J Appl Polm Sci 2010;118:2342‐2349.

Savas H, Guven O. Investigation of active substance release from

poly (ethylene oxide) hydrogels. Int J Pharm 2001;224:151‐158.

Asian Journal of Pharmaceutics - July-September 2013

Sudhakar, et al.: Microspheres for in vitro release studies

Allen C, Han J, Yu Y, Maysinger D, Eisenberg A. Polycaprolactone–

b‐poly (ethylene oxide) copolymer micelles as a delivery vehicle for

dihydrotestosterone. J Control Release 2005;63:275‐286.

Zeng Y, Pitt WG. Poly (ethylene oxide)‐b‐poly (N‐isopropylacrylamide)

nanoparticles with cross‐linked cores as drug carriers. J Biomater Polym

Ed 2005;3:371‐380.

Chiappetta DA, Sosnik A. Poly (ethylene oxide)–poly (propylene

oxide) block copolymer micelles as drug delivery agents: Improved

hydrosolubility, stability and bioavailability of drugs. Eur J Pharm

Biopharm 2007;66:303‐317.

Kiss D, Suvegh K, Zelko R. The effect of storage and active ingredient

properties on the drug release profile of poly (ethylene oxide) matrix

tablets. Carbo Polym 2008;74:930‐933.

Pathak JA, Colby RH, Kamath SY, Kumar SK, Stadler R. Rheology of

miscible blends: SAN and PMMA. Macromolecules 1998;31:8988‐8997.

Hamon L, Grohens Y, Soldera A, Holl Y. Miscibility in blends of

stereoregular poly (methyl methacrylate)/poly‐(ethylene oxide) based

oligomers. Polym 2001;42:9697‐9703.

Machado JC, Silva CG, Soares LS. Positron annihilation and differential

scanning calorimetry investigations in poly (methyl methacrylate)/low

molecular weight poly (ethylene oxide) polymer blends. J Polym Sci B

;38:1045‐1052.

Lisowski MS, Liu Q, Cho JD, Runt J, Yeh F, Hsiao BS. Crystallization

behaviour of poly (ethylene bride) and its blends using time‐resolved

wide‐ and small‐angle X‐ray scattering. Macromolecules

;33:4842‐4849.

Baldrian J, Horky'M, Sikora A, Steinhart M, Vlcˇek P, Amenitsch H, et al.

Time‐resolved SAXS study of crystallization of poly (ethylene oxide)/

poly (methyl methacrylate) blends. Polym 1999;40:439‐445.

Schantz S. Structure and mobility in poly (ethylene oxide)/

poly (methyl methacrylate) blends investigated by 13C solidstate NMR.

Macromolecules 1997;30:1419‐1425.

Lartigue C, Guillermo A, Cohen‐Addad JP. Proton NMR investigation

of the local dynamics of PEO in PEO/PMMA blends. J Polym Sci B

;35:1095‐1105.

Zawada JA, Ylitalo CM, Fuller GG, Colby RH, Long TE. Component

relaxation dynamics in a miscible polymer blend: Poly (ethylene oxide)/

poly (methyl methacrylate). Macromolecules 1992;25:2896‐2902.

Ito H, Russell TP, Wignall GD. Interactions in mixtures of

poly (ethylene oxide) and poly (methyl methacrylate). Macromolecules

;20:2213‐2220.

Silvestre C, Cimmino S, Martuscelli E, Karasz FE, MacKnight WJ.

Poly (ethylene oxide)/poly (methyl methacrylate) blend: Influence of

toxicity of poly (methyl methacrylate) on blend structure and miscibility.

Polym 1987;28:1190‐1199.

Rao GR, Castiglioni C, Gussoni M, Zrbi G, Martuscelli E. Probing the

structure of polymer blends by vibrational spectroscopy: The case of

poly (ethylene oxide) and poly‐ (methyl methacrylate) blends. Polym

;26:811‐820.

Davis R, Brogden RN. Nimesulide: An update of its pharmacodynamic

and pharmacokinetic properties and therapeutic efficacy. Drugs

;48:431‐454.

Meriani F, Coceani N, Sirotti C, Voinovich V, Grassi M. Characterization

of a quaternary liquid system improving the bioavailability of poorly

water soluble drugs. J Colloid Interface Sci 2003;263:590‐596.

Piel G, Pirotte B, Delneuveille I. Neven P, Llabres G, Delarge J, et al.

Study of the Influence of both Cyclodextrins and L‐lysine on the

Aqueous Solubility of Nimesulide: Isolation and Characterization

of Nimesulide‐L‐lysine‐cyclodextrin Complexes. J Pharm Sci

;86:475‐480.

Ferreira SH. Role of interleukins and nitric oxide in the mediation

of inflammatory pain and its control by peripheral analgesics. Drugs

;46:1‐9.

Tognella S, Nimesulide: New clinical opportunities. Drugs

;46:275‐276.

Verhoeven AJ, Tool AT, Kuijpers TW, Roos D. Nimesulide inhibits

platelet‐activating factor synthesis in activated human neutrophils.

Drugs 1993;46:52‐58.

Ravikumara NR, Madhusudhan B, Nagaraj TS, Hiremat SR, Raina G.

Preparation and evaluation of nimesulide‐loaded ethylcellulose and

methylcellulose nanoparticles and microparticles for oral delivery.

J Biomater Appl 2009;24:47‐64.

Dutet J, Lahiani MS, Didier L, Jezequel S, Bounoure F, Barbot C, et al.

Nimesulide/cyclodextrin/PEG 6000 ternary complexes: Physico‐chemical

characterization, dissolution studies and bioavailability in rats. J Incl

Phenom Macrocycl Chem 2007;57:203‐209.

Singla AK, Chawla M, Singh A. Nimesulide: Some pharmaceutical

and pharmacological aspects and update. J Pharm Pharmacol

;52:467‐486.

Paul AI, Hardman JG, Limbird LE, Molinoff PB, Ruddon WR, Gilman AG,

editors. Goodman and Gilman’s. The Pharmacological basis of

therapeutics, chapter, Drugs Affecting Renal and Cardiovascular

Function. 9th ed. New York: McGraw‐Hill Companies, Inc.; 1996. p. 644.

Jacobsen J. Buccal iontophoretic delivery of atenolol.·HCl employing

a new in vitro three‐chamber permeation cell. J Control Release

;70:83‐95.

Ritger PL, Peppas NA. Simple equation for description of solute release.

II. Fickian and anomalous release from swellable devices. J Control

Release 1987;5:37‐42.




DOI: http://dx.doi.org/10.22377/ajp.v7i3.18

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