FORMULATION AND EVALUATION OF DIAZEPAM-LOADED INTRAVAGINAL ALGINATE BEADS: AN INVESTIGATION STUDY FOR THE TREATMENT OF PELVIC FLOOR DYSFUNCTION
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i7.25213Keywords:
Diazepam, Intravaginal alginate beads, Ionotropic gelation, Pelvic floor dysfunctionAbstract
Objective: The fundamental objective of this research investigation was to develop intravaginal diazepam (DZ)-loaded alginate beads for the management of acute pelvic floor dysfunction (PFD) pain with minimal sedative effect.
Methods: DZ loaded beads were prepared by an ionotropic gelation method using SA (sodium alginate) alone, or in combination with either poloxamer 407 (PL), pectin (PC), or xanthan gum (XG) at different ratios in the presence of different concentrations of calcium chloride as a cross-linking agent. The successfully developed beads were evaluated for the particle size, pH, yield percentage, entrapment efficiency, in vitro bioadhesion, swelling percentage, and in vitro drug release. The stability, ex vivo drug permeation, and sedative action of the optimized beads formulations were studied.
Results: The particle size of the formulated beads was from 395±3.3 to 515±2.8 μm, yield percentage was from 68.2±1.7 to 87.5±2.1, entrapment efficiency was from 65.6±1.6 to 87.5±2.1. pH ranged from 6.1±0.2 to 6.8±0.6, bioadhesion strength was from 71.5±1.3 to 87.6±3.1, and swelling percentage was in the range from 53.4±3.1 to 85.2±3.7. Approximately 92.4–72.6% of the loaded dose was released from the prepared beads. The optimized beads showed a good stability under the selected storage conditions. About 74.8%, 71.1%, 68.6%, and 63.4% of the loaded dose permeated through the rabbit vaginal mucosa from F7, F9, F3, and F11, respectively. The formulated beads decreased the sedative action associated with orally or parenterally administered DZ.
Conclusion: The developed beads were considered a promising candidate to formulate DZ into a new dosage form for the treatment of PFD with a minimum central nervous system sedation.
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References
Acartürk F. Mucoadhesive vaginal drug delivery systems. Recent Patents Drug Deliv Form 2009;3:193-5.
Friend DR. Advances in vaginal drug delivery. Drug Deliv Transl Res 2011;1:183-4.
Kalita B, Saikia K, Kalita B. Formulation and evaluation of metronidazole microspheres-loaded bioadhesive vaginal gel. Asian J Pharm Clin Res 2017;10:418-24.
Kurana S, Madav NV. Review article on mucoadhesive drug delivery; Mechanism and method of evaluation. Int J Pharm Bio Sci 2011;2:458 67.
Sharma M, Jain K, Dev SK, Choudhury PK. Formulation and evaluation of sodium alginate beads by emulsion gelation method. Asian J Pharm 2017;11:101-6.
Sharma M, Choudhury PK, Dev SK. Formulation and in-vitro-in-vivo evaluation of alginate-chitosan microspheres of glipizide by ionic gelation method. Asian J Pharm Clin Res 2017;10:385-90.
Abdellatif AA, El Hamd MA, Saleh K. A formulation, optimization and evaluation of controlled released alginate beads loaded-flurbiprofen. J Nanomed Nanotechnol 2016;7:1-8.
Abass HA, Kamel R. Formulation and evaluation of in situ forming polymeric drug delivery systems for mixed vaginal infection. Br J Pharm Res 2014;4:2281-95.
Boyadzhyan L, Raman SS, Raz S. Role of static and dynamic MR imaging in surgical pelvic floor dysfunction. Radiographics 2008;28:949-67.
Hagen S, Stark D. Conservative prevention and management of pelvic organ prolapse in women. Cochrane Database Syst Rev 2011;12:CD003882.
Rogalski MJ, Kellogg-Spadt S, Hoffmann AR, Fariello JY, Whitmore KE. Retrospective chart review of vaginal diazepam suppository use in high-tone pelvic floor dysfunction. Int Urogynecol J Pelvic Floor Dysfunction 2010;21:895-9.
Capra P, Perugini P, Bleve M, Pavanetto P, Musitelli G, Rovereto B, et al. Innovative approach for interstitial cystitis: Vaginal pessaries loaded diazepam—a preliminary study. J Pharm 2013;2013:1-7.
Balkis AK. The release of diazepam from different conventional and hollow type suppository bases. Iraqi J Pharm Sien 2007;16:21-5.
Khan AD, Bajpai M. Formulation and evaluation of floating beads of verapamil hydrochloride. Int J PharmTech Res 2011;3:1537-46.
Rasel MA, Hasan M. Formulation and evaluation of floating alginate beads of diclofenac sodium. Dhaka Univ J Pharm Sci 2012;11:29-35.
Ranvirsingh TA, Basavaraj BV, Bharath S, Deveswaran R, Madhavan V. Formulation and evaluation of floating alginate beads of an anti ulcer drug. Int J Pharm Sci Rev Res 2013;21:120-4.
Sruthi A, Tejaswi P, Thanuja N, Kumar DS, Sagar PV. Simple RP-HPLC method for estimation of diazepam in tablet dosage form. J Pharm Res 2013;6:140-4.
Jaiswal D, Bhattacharya A, Yadav IK. Formulation and evaluation of oil entrapped floating beads of ranitidine hydrochloride. Int J Pharm Pharm Sci 2009;1:128-40.
Tiwari RK, Singh L, Sharma V. Performance optimization of sustained release arginine alginate microbeads with a natural polysaccharide. J Pharm Res Int 2017;17:1-11.
Parhi R, Suresh P. Alginate-poloxamer beads for controlled release of metoprolol succinate. Turk J Pharm Sci 2012;12:59-66.
Velmurugan S, Ali MA. Formulation and evaluation of maraviroc mucoadhesive microsheres by ionotropic gelation method. Int J Pharm Pharm Sci 2013;5:294-2.
Aziz A, Khan IA. Pharmacological evaluation of sedative and hypnotic activities of methanolic extract of Lycopus europaeus in mice. J Phytopharmacol 2013;2:8-12.
Courvoisier S, Ducrot R, Julou L, Garattini S, Ghetti V, editors. Psychotropic Drugs. Amsterdam: The Netherlands; 1957.
Clark G, Koester AG, Pearson DW. Exploratory behavior in chronic disulfoton poisoning in mice. Psychopharmacologia 1971;20:169-71.
Patel YL, Sher P, Pawar AP. The effect of drug concentration and curing time on processing and properties of calcium alginate beads containing metronidazole by response surface methodology. AAPS PharmSciTech 2006;7:86.
Das S, Samanta A, Bose A. Design, development and evaluation of fluconazole topical gel. Asian J Pharm Clin Res 2015;8:132-5.
Kashid P, Doijad R, Shete A, Sajan S, Bhagat A. Studies on rebamipide loaded gastroretentive alginate based mucoadhesive beads: Formulation and in-vitro, in-vivo evaluation. Pharm Methods 2016;7:132-8.
Manjanna KM, Shivakumar B, Pramod KT. Formulation of oral sustained release aceclofenac sodium microbeads. Int J Pharm Tech Res 2009;1:940-52.
Akifuddin SK, Abbas Z, Marihal S, Ranadev AK, Kumar SI, Kulkarni R. Preparation, characterization and in-vitro evaluation of microcapsules for controlled release of diltiazem hydrochloride by ionotropic gelation technique. J Appl Pharma Sci 2013;3:35-42.
Sankula K, Kota S, Rao N. Formulation and evaluation of nizatidine mucoadhesive microspheres by ionic-gelation method. Eur J Pharm Sci Res 2014;1:3-9.
Pal R, Bhadoria AP, Ramteke S. Preparation and characterization of sodium alginate-Cbp-934P based mucoadhesive microbeads. Scholars Res Lib Pharm Lett 2011;3:1-1.
Jelvehgari M, Valizadeh H, Motlagh RJ, Montazam H. Formulation and physicochemical characterization of buccoadhesive microspheres containing diclofenac sodium. Adv Pharm Bull 2014;4:295-1.
Iswariya VT, Soujanya GL, Santhosh R, Kumar AP, Lingaswamy J, Satyanarayana K. Design and development of in vitro characterization of floating microspheres of ranolazine. Eur J Pharm Med Res 2016;3:220-32.
Swetha R, Baru CR, Vidyadhara S, Prakash KV. Formulation and evaluation of celecoxib bioadhesive microspheres. Indo Am J Pharm Sci 2014;1:407-19.
Jahan S, Sadat SM, Islam MR, Azam AT, Chowdhury JA. Effect of various electrolytes on theophylline loaded sodium alginate beads prepared by ionic cross linking technique. Dhaka Univ J Pharm Sci 2012;11:181-9.
Mane S, Ponrathnam S, Chavan N. Effect of chemical cross-linking on properties of polymer microbeads: A review. Canadian Chem Trans 2015;3:473-85.
Gavini V, Ragini B, Kaumudi K. Mucoadhesive microspheres-a novel approach of drug targeting. World J Pharm Pharm Sci 2014;3:310-35.
Chickering DE, Mathiowitz E. Bioadhesive microspheres: I. a novel electrobalance-based method to study adhesive interactions between individual microspheres and intestinal mucosa. J Control Rel 1995;34:251-61.
Rajinikanth PS, Sankar C, Mishra B. Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: Development and evaluation. Drug Deliv 2003;10:21-8.
Maddiboyina B, Asthana A, Asthana GS, Singh S, Ramya M, Sunnapu O, et al. Formulation and characterization of polycarbophil coated mucoadhesive microspheres of repaglinide. J Pharm Sci Res 2015;7:972-7.
Mandal S, Kumar SS, Krishnamoorthy B, Basu SK. Development and evaluation of calcium alginate beads prepared by sequential and simultaneous methods. Braz J Pharm Sci 2010;46:785-93.
Kulkarni N, Wakte P, Naik J. Development of floating chitosan-xanthan beads for oral controlled release of glipizide. Int J Pharm Investig 2015;5:73-80.
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