Abstract
The purpose of present work was to develop suppositories containing mucoadhesive microspheres of granisetron hydrochloride (GH) using combination of xanthan gum and sodium alginate. Twelve different batches of microspheres containing GH were prepared by simple emulsification method and evaluated for surface morphology, particle size, equilibrium swelling degree, drug content, in vitro mucoadhesion, and in vitro drug release. The suppositories containing optimized batch of microspheres (C2) were formulated by fusion method using hydrophilic and lipophilic polymer base. The suppositories were evaluated for weight variation, hardness, macromelting range, drug content, drug release, morphology of rectal tissues, and in vivo suppository localization. Results show that, all microsphere batches were spherical and had size range 23.56–36.76 μm. The % drug encapsulation was found in the range 61.67–92.30 %, and showed satisfactory mucoadhesion. Especially, C2 batch had 83.67 % mucoadhesion and 92.30 % drug encapsulation and showed release retardation for 4 h. The results of all suppositories were within the pharmacopoeial standard limits. Drug content of all the suppositories was in the range 93.20–98.40 %. The suppository batch (P2M) was considered best on the basis of optimum retardation up to 5 h, high drug content, optimum mechanical strength and zero order release (r2 = 0.9860). The suppository of batch P2M showed no morphological changes in rectal tissues indicating its safety. In vivo localization revealed satisfactory mucoadhesion of microspheres. Hence, it can be concluded that, delivery of GH in suppository form can avoid its presystemic metabolism, thus, may be an efficient alternative to its oral dosage form and conventional suppository.
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References
Bain DF, Munday DL, Smith A (1999) Solvent influence on spray dried biodegradable microspheres. J Microencapsulation 16:453–474
Baker R (1987) Introduction. In: Baker R (ed) Controlled release of biologically active agents, vol 15. Wiley-Interscience Publication, New York, pp 1–18
Bertram U, Bodmeier R (2006) In situ gelling bio adhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form. Eur J Pharm Sci 27:62–71
Burgess DJ, Hickey AJ (2005) Microspheres: design and manufacturing. In: Burgess DJ (ed) Injectable dispersed systems: formulation, processing and performance, vol 149. Taylor & Francis, Boca Raton, pp 305–353
Choi HG, Ohb YK, Kima YI, Kima JO, Yoo BK, Rheea JD (2005) Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats. Int J Pharm 301:54–61
Davidovich-Pinhas M, Bianco-Peled H (2010) A quantitative analysis of alginate swelling. Carbohyd Polym 79:1020–1027
Denkbas ED, Seyyal M, Piskins E (1999) 5-fluorouracil loaded chitosan microspheres for chemoembolization. J Microencapsulation 16:741–749
Dollary C (1999) Therapeutic drugs, part I, 2nd edn. Churchill Livingstone, London, pp 86–90
Hamdi G, Ponchel G (1999) Enzymatic degradation of epichlorhydrin crosslinked starch microspheres by α-amylase. Pharm Res 16:867–875
Kikuchi A, Kawabuchi M, Sugihara M, Sakurai Y, Okano T (1997) Pulsed dextran release from calcium–alginate gel beads. J Control Rel 47:21–29
Korsmeyer RW, Gurny R, Docler E, Buri P, Peppas NA (1983) Mechanism of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35
Mandal TK, Bostanian LA, Graves RA, Chapman SR, Idodo TU (2001) Porous biodegradable microparticles for delivery of pentamidine. Eur J Biopharm 52:91–96
Ostberg T, Lund EM, Graffner C (1994) Calcium alginate matrices for oral multiple unit administration: IV. Release characteristics in different media. Int J Pharm 112:241–248
Peter A, Watkinson AC, Foley, Lardner LLP (2006) San Diego, USPTO Patent Application 20060177493
Pongjanyakul T, Puttipipatkhachorn S (2007) Xanthan–alginate composite gel beads molecular interaction and in vitro characterization. Int J Pharm 331:61–71
Rajnikanth PS, Sankar C, Mishra B (2003) Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: development and evaluation. Drug Deliv 10:21–28
Rastogi R, Sultana Y, Aqil M, Alib A, Kumarc S (2007) Alginate microspheres of isoniazid for oral sustained drug delivery. Int J Pharm 334:71–77
Sah ML, Saini TR (2008) Formulation development and release studies of indomethacin suppositories. Indian J Pharm Sci 70(4):498–501
Saleem MA, Taher M, Sanaullah S (2008) Formulation and evaluation of tramadol hydrochloride rectal suppositories. Indian J Pharm Sci 70(5):640–644
Swamy PV, Amitkumar T, Shrisand SB, Patil AN (2010) Once-daily sustained-release matrix tablets of metoprolol tartrate : formulation and in-vitro evaluation. Indian J Pharm Educ Res 44:95–101
Tarlmcl N, Ermis D (1997) Sustained release characteristics and pharmacokinetic parameters of ketoprofen suppositories using chitosan. Int J Pharm 147:71–77
Tripathi KD (2003) Essentials of medical pharmacology, vol 146, 5th edn. Jaypee Brothers medical publishers, New Delhi, pp 605–607
Uzunkaya G, Bergis N (2003) In vitro drug liberation and kinetics of sustained release indomethacin suppository. Il Farmaco 58:509–512
Wan LSC, Heng PWS, Chan LW (1992) Drug encapsulation in alginate microsphere by emulsification. J Microencapsulation 9:309–316
Yahagi R, Machida Y, Onishi H, Machida Y (2000) Mucoadhesive suppositories of ramosetron hydrochloride utilizing Carbopol. Int J Pharm 193:205–212
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All authors (N. H. Salunkhe, N. R. Jadhav, K. K. Mali, R. J. Dias, V. S. Ghorpade, A. V. Yadav) declare that they have no conflict of interest. Authors are thankful to Cipla, Mumbai (India) for providing the gift sample of granisetron hydrochloride and the management of Satara College of Pharmacy, Satara for providing the facilities to carry out the work.
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Salunkhe, N.H., Jadhav, N.R., Mali, K.K. et al. Mucoadhesive microsphere based suppository containing granisetron hydrochloride for management of emesis in chemotherapy. Journal of Pharmaceutical Investigation 44, 253–263 (2014). https://doi.org/10.1007/s40005-014-0123-6
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DOI: https://doi.org/10.1007/s40005-014-0123-6