Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24？sec), TS (2.85？N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of (95.87%), (71.42%), (98.125%), and (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles. 1. Introduction Oral route is one of the most preferred routes of drug administration due to its safety, ease of administration, and acceptability by patients. About 60% of conventional dosage forms are available as the oral solid dosage forms [1]. The low bioavailability, longer onset of action, and dysphasia patients turned the manufacturer towards the parenterals and liquid dosage forms. But the liquid dosage forms (syrup, suspension, emulsion, etc.) have the problem of accurate dosing and parenterals are painful drug delivery systems, so they result in patient incompliance. The most popular oral dosage forms are tablets and capsules; one major drawback of these dosage forms is the difficulty to swallow [2]. Drinking water plays an important role in the swallowing of oral dosage forms. People experience inconvenience in swallowing tablet dosage forms when water is not available particularly in the case of traveling (motion sickness) and sudden episodes of coughing during the common cold, allergic condition, and bronchitis. Under such circumstances, tablets that can rapidly dissolve or disintegrate in the oral cavity known as fast dissolving tablets have attracted a great deal of attention. Fast dissolving tablets are also known as mouth-dissolving tablets, orodispersible tablets, rapidmelts, and porous tablets. Fast dissolving tablets dissolve or disintegrate within 60 seconds when placed in the mouth without drinking
References
[1]
A. Arya, A. Chandra, V. Sharma, and K. Pathak, “Fast dissolving oral films: an innovative drug delivery system and dosage form,” International Journal of ChemTech Research, vol. 2, no. 1, pp. 576–583, 2010.
[2]
K. Sharma, W. R. Pfizer, and T. K. Ghosh, “Quick-dispersing oral drug delivery systems,” in Drug Delivery to the Oral Cavity Molecule to Market, vol. 145, pp. 262–287, 2005.
[3]
F. Cilurzo, I. E. Cupone, P. Minghetti, F. Selmin, and L. Montanari, “Fast dissolving films made of maltodextrins,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 70, no. 3, pp. 895–900, 2008.
[4]
S. K. Yellanki, S. Jagtap, and R. Masareddy, “Dissofilm: a novel approach for delivery of phenobarbital; design and characterization,” Journal of Young Pharmacists, vol. 3, no. 3, pp. 181–188, 2011.
[5]
T. Hanawa, “Development of a new and kindly oral dosage form for elderly,” Journal of Pharmaceutical Science and Technology, vol. 13, no. 4, pp. 251–258, 1997.
[6]
H. Goel, P. Rai, V. Rana, and A. K. Tiwary, “Orally disintegrating systems: innovations in formulation and technology,” Recent Patents on Drug Delivery and Formulation, vol. 2, no. 3, pp. 258–274, 2008.
[7]
R. Mishra and A. Amin, “Formulation development of taste-masked rapidly dissolving films of cetirizine hydrochloride,” Pharmaceutical Technology, vol. 33, no. 2, pp. 48–56, 2009.
[8]
H. Shimoda, K. Taniguchi, M. Nishimura et al., “Preparation of a fast dissolving oral thin film containing dexamethasone: a possible application to antiemesis during cancer chemotherapy,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 73, no. 3, pp. 361–365, 2009.
[9]
S. B. Borsadia, D. O'Halloran, and J. L. Osborne, “Quick-dissolving films—a novel approaches to drug delivery,” Drug Development and Delivery, vol. 3, no. 3, pp. 63–66, 2003.
[10]
K. K. Peh and C. F. Wong, “Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties,” Journal of Pharmacy and Pharmceutical Sciences, vol. 2, no. 2, pp. 53–61, 1999.
[11]
C. M. Corniello, “Quick dissolve strips: from concept to commercialization,” Drug Delivery Technology, vol. 6, pp. 68–71, 2006.
[12]
S. Ali and A. Quadir, “High molecular weight povidone polymer-based films for fast-dissolving drug delivery Application,” Drug Delivery Technology, vol. 7, pp. 36–43, 2007.
[13]
K. S. Kulkarni, H. A. Deokule, M. S. Mane, and D. M. Ghadge, “Exploration of different polymers for use in the formulation of oral fast dissolving strips,” Journal of Current Pharmacy Research, vol. 2, pp. 33–35, 2010.
[14]
S. Malke, S. Shidhaye, J. Desai, and V. Kadam, “Oral films-patient compliant dosage form for pediatrics,” Internet Journal of Pediatrics and Neonatology, vol. 11, no. 2, 2010.
[15]
B. Martineau, “A look at fast-dissolving drug delivery systems,” Drug Delivery Technology, vol. 9, no. 4, pp. 36–38, 2009.
[16]
D. L. Keene, S. Whiting, and P. Humphreys, “Clobazam as an add-on drug in the treatment of refractory epilepsy of childhood,” Canadian Journal of Neurological Sciences, vol. 17, no. 3, pp. 317–319, 1990.
[17]
M. J. Mohammed and O. S. Ali, “Clobazam for the treatment of intractable childhood epilepsy,” Saudi Medical Journal, vol. 21, p. 62, 2000.
[18]
T. Higuchi and K. A. Conner, “Phase-solubility techniques,” Advances in Analytical Chemistry and Instrumentation, vol. 4, pp. 117–122, 1965.
[19]
R. Mishra and A. Amin, “Manufacturing techniques of orally dissolving films,” Pharmaceutical Technology, vol. 35, no. 1, pp. 70–73, 2011.
[20]
M. Dhanasree, “Analytical method development and validation of clobazam by using UV spectrophotometric method,” The Experiment, vol. 1, no. 1, pp. 22–28, 2012.
[21]
J. H. Park, K. M. Holman, G. A. Bish et al., “An alternative to the USP disintegration test for orally disintegrating tablets,” Pharmaceutical Technology, vol. 32, no. 8, pp. 54–58, 2008.
[22]
S.-Y. Lin, “Effect of excipients on tablet properties and dissolution behavior of theophylline-tableted microcapsules under different compression forces,” Journal of Pharmaceutical Sciences, vol. 77, no. 3, pp. 229–232, 1988.
[23]
J. G. Wagner, “Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules.,” Journal of Pharmaceutical Sciences, vol. 58, no. 10, pp. 1253–1257, 1969.
[24]
T. Higuchi, “Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices,” Journal of pharmaceutical sciences, vol. 52, pp. 1145–1149, 1963.
[25]
R. P. Dixit and S. P. Puthli, “Oral strip technology: overview and future potential,” Journal of Controlled Release, vol. 139, no. 2, pp. 94–107, 2009.
[26]
I. S. Chronakis, “On the molecular characteristics, compositional properties, and structural-functional mechanisms of maltodextrins: a review,” Critical Reviews in Food Science and Nutrition, vol. 38, no. 7, pp. 599–637, 1998.
[27]
R. Khanna, S. P. Agarwal, and A. Ahuja, “Preparation and evaluation of muco-adhesive buccal films of clotrimazole for oral Candida infections,” Indian Journal of Pharmaceutical Sciences, vol. 59, no. 6, pp. 299–305, 1997.
[28]
M. E. Aulton, M. H. Abdul-Razzak, and J. E. Hogan, “The mechanical properties of hydroxypropylmethylcellulose films derived from aqueous systems. Part 1: the influence of plasticisers,” Drug Development and Industrial Pharmacy, vol. 7, no. 6, pp. 649–668, 1981.
[29]
P. Venkatesh, R. Rajesh Kumar, A. Rajasekaran, and D. J. Dharman, “Bioanalytical method development and comparative bioavailability study of clobazam tablets in albino rats plasma using RP-HPLC method,” Digest Journal of Nanomaterials and Biostructures, vol. 5, no. 2, pp. 403–409, 2010.
[30]
M. Rezarouini, Y. Ardakani, M. Shohrati, and L. Hakemi, “Pharmacokinetic and bioequivalence study of clobazam 10 mg tablet,” International Journal of pharmacology, vol. 2, pp. 409–481, 2001.
[31]
D. A. El-Setouhy and N. S. A. El-Malak, “Formulation of a novel tianeptine sodium orodispersible film,” AAPS PharmSciTech, vol. 11, no. 3, pp. 1018–1025, 2010.
[32]
N. B. Modi, M. Dakshina, S. Gangadhar, and Y. David, “In vitro–in vivo correlation,” in Pharmaceutical Product Development, pp. 107–123, Informa healthcare, London, UK, 1st edition, 2007.
[33]
P. K. Kulkarni, M. Dixit, K. Gunashekara, A. Shahnawaz, M. N. Singh, and A. Kulkarni, “Formulation and evaluation of mouth dissolving film containing Rofecoxib,” International Research Journal of Pharmacy, vol. 2, pp. 177–178, 2010.
[34]
V. Y. Londhe and K. B. Umalkar, “Formulation development and evaluation of fast dissolving film of telmisartan,” Indian Journal of Pharmaceutical Sciences, vol. 74, no. 2, pp. 122–126, 2012.
[35]
P. Prabhu, R. Malli, M. Koland et al., “Formulation and evaluation of fast dissolving films of levocitirizine dihydrochloride,” International Journal of Pharmaceutical Investigation, vol. 1, no. 2, pp. 99–104, 2011.
[36]
R. Ilango, S. Kavimani, A. R. Mullaicharam, and B. Jayakar, “In vitro studies on buccal strips of glibenclamide using chitosan,” Indian Journal of Pharmaceutical Sciences, vol. 59, no. 5, pp. 232–235, 1997.
[37]
B. K. Satishbabu and B. P. Srinivasan, “Preparation and evaluation of buccoadhesive films of atenolol,” Indian Journal of Pharmaceutical Sciences, vol. 70, no. 2, pp. 175–179, 2008.
