FORMULATION AND EVALUATION OF LORAZEPAM ENCAPSULATED COLLAGEN/PECTIN BUCCAL PATCH

LAKSHMI V. S.; REVATHY B. MENON; KEERTHANA RAJU; AISWARYA M. U.; SREEJA C. NAIR

doi:10.22159/ijap.2019v11i5.34366

Authors

LAKSHMI V. S. Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
REVATHY B. MENON Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
KEERTHANA RAJU Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
AISWARYA M. U. Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
SREEJA C. NAIR Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India

DOI:

https://doi.org/10.22159/ijap.2019v11i5.34366

Keywords:

Lorazepam, Buccal patch, In vitro drug release, Steady state flux, Epileptic seizures

Abstract

Objective: To formulate and characterize Lorazepam loaded buccal patches using mucoadhesive, biodegradable, natural polymers-pectin (hydrophilic) and collagen (lipophilic) for treating epileptic seizures.

Methods: Lorazepam loaded buccal patches were prepared by solvent casting method and were subjected to various Physico-chemical evaluation parameters to find the optimized buccal patch. The in vitro drug release study and ex vivo permeation study was carried out. The stability study and histopathological study of optimized Lorazepam loaded buccal patch was also carried out.

Results: From in vitro drug release study, it was found that Lorazepam loaded buccal patch (B4) exhibited maximum drug release of 96.16 %±0.07 than other formulations at the end of 4 h, indicating an initial burst release followed by sustained release with release kinetics as Higuchi diffusion model. Based on the in vitro drug release, % drug content, % swelling index, folding endurance, B4 formulation was considered as optimised formulation and was further characterized. Ex vivo permeation study revealed that the cumulative amount of drug permeated from optimised Lorazepam loaded buccal patch (B4) was higher (3831.4±0.21µg/cm²) than marketed Midazolam buccal solution (1724±0.12 µg/cm²) and control drug solution (895.42±0.07 µg/cm²) with an enhancement ratio of 4.8. B4 formulation also showed a higher flux value (12.52±0.02µg/cm²/hr) compared to marketed formulation (5.732±0.01 µg/cm²) and control drug solution (2.563±0.03 µg/cm²) of P<0.05. The histopathological study using bovine buccal mucosa revealed that the B4 formulation is safe for buccal application. The stability study confirmed that B4 formulation is stable in both room and refrigeration conditions. Hence the formulated Lorazepam loaded buccal patch seems to be a promising carrier for the enhanced buccal delivery of Lorazepam in treating epileptic seizures.

Conclusion: The formulated Lorazepam loaded collagen/pectin buccal patch was found to be an efficient and stable route for the buccal delivery of Lorazepam in treating acute epileptic seizures which could be further explored scientifically.

Downloads

Download data is not yet available.

References

Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia 1979;20:729-37.

Arroyo S, Kramer G. Treating epilepsy in the elderly: safety considerations. Drug Saf 200;24:991-1015.

Desai C. Meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions. Indian J Pharmacol 2016;48:224.

Mark M. Recent advances in epilepsy. J Neurol 2017;264:1811-24.

Suruchi S, Vaishali D. Epilepsy-a comprehensive review. Int J Pharm Res Rev 2013;2:61-80.

Khanna R, Agarwal SP, Ahuja A. Mucoadhesive buccal delivery: a potential alternative to conventional therapy. Indian J Pharm Sci 1998;60:1-11.

Sudhir M, Buchi NN. Development of zolmitriptan mouth dissolving films: formulation, mechanical properties and in vitro drug release studies. Asian J Pharm Clin Res 2019;12:273-9.

Madhavi BR, Murthy VSN, Rani AP, Kumar GD. Buccal film drug delivery system: an innovative and emerging technology. J Mol Pharm Org Process Res 2013;1:107.

Reddy RJ, Anjum M, Hussain MA. A comprehensive review on buccal drug delivery system. Am J Adv Drug Delivery 2013;1:300-12.

Michael R, Joseph E, Guido B, Frank A. Oral mucosa harvest: an overview of anatomic and biologic consideration. EAU-EBU Update Series; 2007. p. 179-87.

Verma P, Thakur S, Deshmukh K, Verma S. Routes of drug administration. Int J Pharm Sci Res 2010;1:54-109.

Sellappan V, Sumanjali D. Buccal penetration enhancers-an overview. Asian J Pharm Clin Res 2013;6:39-47.

Harris D, Robinson JR. Drug delivery via the mucous membranes of the oral cavity. J Pharm Sci 1992:81:1-10.

Lester DR Thompson. Data set for the reporting of oral cavity carcinoma. Arch Pathol Lab Med 2019;143:439-46.

Ali AMA, Sarhan HA, Magdy T. Preparation and characterization of phenytoin sodium niosomes for enhanced closure of skin injuries. Int J Pharm Pharm Sci 2014;6:542-6.

Sanket D, Priyanka R, Rahul U, Tanvi T, Manoj A. Mucoadhesive drug delivery systems-an unusual maneuver for site-specific drug delivery system. Int J Pharm Sci 2011;2:132-52.

Surya N, Adhikari R, Bhabani SN, Amit K, Mohanty B. Formulation and evaluation of buccal patches for delivery of atenolol. AAPS PharmSciTech 2010;11:1038-44.

Smart DJ. Drug delivery using buccal adhesive systems. Adv Drug Delivery Rev 1993;11:253-70.

Shinkar DM, Dhake AS, Setty CM. Drug delivery from the oral cavity: A focus on mucoadhesive buccal drug delivery systems. J Pharm Sci Tech 2012;66:466-500.

Pankil GA, Patel MR, Patel NM. A review article on mucoadhesive buccal drug delivery system. Int J Pharm Res Dev 2011;3:159-73.

Patel KV, Patel KR, Patel MR, Patel NM. A review article on mucoadhesive buccal drug delivery system: an overview. Int J Pharm Bio Arch 2011;2:600-9.

Amir HS. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci 1998;1:15-30.

Felipe PF, Amanda CF, Said GCF, Jorg B, Humberto GF. Manufacture and characterization of mucoadhesive buccal films based on pectin and gellan gum containing triamcinolone acetonide. Int J Polym Sci 2018;1:1-10.

Bindu MB, Zulkar NK, Ravinder N, David B. Mucoadhesive drug delivery system: an overview. J Adv Pharm Tech Res 201;1:381-407.

Priya VB, Kanchan P, Upadhye, Gouri D. Formulation and evaluation of fast dissolving oral melt-in-mouth of Lorazepam for sublingual use. J Pharm Pharm Sci 2016;5:763-75.

Jaleh V, Farzin F, Erfaneh G. Formulation optimization and in vitro evaluation of rapid disintegrating and mucoadhesive sublingual tablets of lorazepam. Formacia 2015;63:234-45.

Navneet V, Pronobesh C. Preparation of mucoadhesive patches for buccal administration of metoprolol succinate: in vitro and in vivo drug release and bioadhesion. Trop J Pharm Res 2012;11:9-17.

Gathwala G, Goel M, Singh J, Mittal K. Intravenous diazepam, midazolam and lorazepam in acute seizure control. Indian J Pediatr 2012;79:327-32.

Aswathy N, Vidhya KM, Saranya TR, Sreelakshmy KR, Sreeja CN. Mucoadhesive buccal patch of cefixime trihydrate using biodegradable natural polymer. Int J Pharm Sci 2014;6:366-71.

Gomez Guillen MC, Begona G, Lopenz Cabullero ME, Montero P. Functional and bioactive properties of collagen and gelatine from alternative sources: a review. Foodhyd 2011;25:1813-27.

Puglia C, Bonina F, Trapuni G, Franco M, Ricci M. Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from hydroalcoholic gel formulations. Int J Pharm 2001;28:79-87.

Nazila SM, Montakarn C, Thomas PJ. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Delivery Rev 2005;57:1661-91.

Presland RB, Dale BA. Epithelial structural proteins of the skin and oral cavity: functionin health and disease. Crit Rev Oral Biol Med 2000;11:383-408.

Walker DM. Oral mucosal immunology: an overview. Ann Acad Med Singapore 2004;33:27-30.

Wolfgang W, Natalie L, Claudia M, Alexander W, Michal S. Identification of lorazepam and slidenafil as examples for the application of LC/ionspray-MS and MS-MS with mass spectra library searching in forensic toxicology. Forensic Sci Int 2000;113:339-44.

Nafee NA, Boraie MA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharmaceutica 2003;53:199-212.

Nafee NA, Ismail FA, Mortada LM, Boraie MA. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of aging. Int J Pharm 2003;264:1-14.

Burgalassi S, Panichi L, Saettone MF, Jacobsen J, Rassing MR. Development and in vitro/in vivo testing of mucoadhesive buccal patches releasing benzydamine and lidocaine. Int J Pharm 1996;133:1-7.

Vishnu MP, Bhupendra GP, Madhabhai MP. Design and characterization of chitosan containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharma 2007;57:61-72.

Patel RS, Poddar SS. Development and characterization of mucoadhesive buccal patches of salbutamol sulfate. Curr Drug Delivery 2009;6:140-4.

Kaur A, Kaur G. Mucoadhesive buccal patches based on interpolymer complexes of chitosan-pectin for delivery of carvedilol. Saudi Pharm J 2012;20:21-107.

Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Cappuccella M, et al. Development of mucoadhesive patches for buccal administration of ibuprofen. J Controlled Release 2004;99:73-82.

Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm 2011;77:187-99.

Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films of glipizide. Indian J Pharm Sci 2008;70:43-108.

Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive delivery systems I Evaluation of mucoadhesive polymers for buccal tablet formulation. Drug Dev Ind Pharm 2004;30:985-93.

Gupta A, Garg S, Roop Krishen K. Measurement of bioadhesive strength of mucoadhesive buccal tablets: design of an in vitro assembly. Indian Drugs 1993;30:152-5.

Deepak S, Dipika M, Gilphy P, Ravish R, Shanu B, Manisha S, et al. Formulation and optimization of nanoparticles for intranasal delivery of lorazepam using box-Behnken design: in vitro and in vivo evaluation. Bio-Med Res Int 2014:14. http://dx.doi.org/10.1155/2014/156010

Amit AK, Vandana BP. Development and evaluation of lorazepam microemulsions for parenteral delivery. AAPS PharmSciTech 2008;9:966-71.

Trissel LA, Xu QA. Physical and chemical stability of palonosetron hydrochloride with lorazepam and midazolam hydrochloride during stimulated Y-Site administration. Int J Pharm Compd 2005;9:235-307.

Ataurrahmann F, Rsale, Ansari H. Formulation development and evaluation of flexible polymeric topical antifungal film. Int J adv Pharm Med Bioallied Sci 2015;3:137-41.

Foox M, Zilberman M. Drug delivery from gelatine based systems. Expert Opin Drug Delivery 2015;12:1547-63.

Sahar S, Soheli B. New formulation and approach for a mucoadhesive buccal film of rizatriptan benzoate. Prog Biomater 2017;6:175-87.

Ashutosh R, Prabhakara P, Akhilesh D. Design and evaluation of buccal patches containing combination of hydrochlorothiazide and atenolol. Int J Appl Pharm 2018;10:105-12.

Parmar VJ, Lumbhani AN, Vijayalakshmi P, Sajal J. Formulation development and evaluation of buccal films of carvedilol. Int J Pharm Sci Res 2010;1:149-56.

Lakshmana MG, Raghuvamsi V, Tirumala devi N, Narendra B, Sravya C, Masthaniah K, et al. Design and evaluation of diclofenac sodium buccal mucoadhesive film by solvent casting technique. Int J Pharm Sci Res 2014;5:1767-75.

Gorakh JD, Durgacharan AB, John ID. Formulation and evaluation of fast dissolving buccal patch of olmesartan medoxomil. Asian J Biomed Pharm Sci 2013;3:51-5.

Himabindhu P, Krishna MC, Nagaraj B. Design and in vitro characterization of mucoadhesive buccal patches of duloxetine. Int J Pharm Pharm Sci 2017;9:52.

Marina K, Narayana C, Vijayanarayana K, Prabhakara P. In vitro and In vivo evaluation of chitosan buccal films of ondansetron hydrochloride. Int J Pharm Investig 2011;1:164-71.

Indira M, Srujana K. Mucoadhesive buccal films of glibenclamide: development and evaluation. Int J Pharm Investig 2011;1:42-57.

Raghavendra R, Sunil F, Keyur P. Formulation and in vitro evaluation of mucoadhesive buccal patches containing zolmitriptan using gel-forming polymers. Der Pharmacia Sinica 2012;3:47-57.

Sumendra B, Mayank B, Gopal G. Preparation and evaluation of buccoadhesive patches of an antihypertensive drug. Am J Phytomed Clin Ther 2013;1:240-55.

Pooja S, Dharmendra S. Formulation and evaluation of mucoadhesive buccal patch of timolol maleate. Am J Pharm Tech Res 2017;7:335-48.

Shivhare UD, Vyawahare AM, Bodele SB. Formulation and evaluation of mucoadhesive buccal patch for the treatment of migraine. Int J Pharm Chem Biol Sci 2013;2:1812-8.

Pradeep KK. Formulation and in vitro evaluation of bilayered buccal patches of a proton pump inhibitor. Am J Adv Drug Delivery 2013;1:651-62.

Sreeja CN, Mabble SJ, Anoop KR. In situ gel: an innovative approach for safe and sustained nasal drug delivery. Int J Pharm Sci Rev 2014;24:1-7.

Aiswarya MU, Keerthana R, Revathy BM, Lakshmi VS, Sreeja CN. Cryptosomes: A revolutionary breakthrough in novel drug delivery. Int J Appl Pharm 2019;11:7-13.

Revathy BM, Lakshmi VS, Aiswarya MU, Keerthana R. Porphysomes-a paradigm shift in targeted drug delivery. Int J Appl Pharm 2018;10:1-6.

Paul A, Fathima M, Nair SC, Antony NV. Intranasal in situ gelling system of lamotrigine using ion activated mucoadhesive polymer. Open Med Chem J 2017;11:222-44.