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Dharamsi, Abhay
- Development and Evaluation of a Polyherbal Tablet for Polycystic Ovarian Syndrome (PCOS)
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PDF Views:88
Authors
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1 Parul Institute of Pharmacy and Research, Parul University, Vadodara - 391110, Gujarat, IN
2 Parul Institute of Pharmacy, Parul University, Vadodara - 391110, Gujarat, IN
1 Parul Institute of Pharmacy and Research, Parul University, Vadodara - 391110, Gujarat, IN
2 Parul Institute of Pharmacy, Parul University, Vadodara - 391110, Gujarat, IN
Source
Journal of Natural Remedies, Vol 22, No 2 (2022), Pagination: 160 - 174Abstract
The main objective of the present study was to develop and evaluate polyherbal tablet for the treatment of Polycystic Ovarian Syndrome (PCOS). For the formulation of tablet, the herbs were selected based on the concepts of pathophysiology and Ayurvedic perspective of the disease. The extracts of T. foenum graceum, C. longa, B. aristata, S. asoka, B. variegata and Guggul purified in cow’s urine was used for the preparation of polyherbal tablet. The physicochemical, phytochemical evaluation and quantification of markers by HPTLC of crude drugs and extracts were performed. The guggul was used as binder in different proportion for the preparation of tablet. Pre-formulation study of the powder blend and post compression evaluation of tablet was done by various parameters like weight variation, friability, hardness, thickness, diameter, disintegration time, in-vitro dissolution and accelerated stability study. The physicochemical evaluations of crude drugs yielded results which were in accordance with the monograph’s standard values. The phytochemical analysis of the extracts revealed the presence of variety of phytoconstituents. From the results of HPTLC quantification the amount of curcumin (7.14%) in C. longa, diosgenin (40.6%) in T. foenum graceum ,T. foenum graceum, berberine hydrochloride (4.83%) in B. aristata, catechin (3.48%) in S. asoka, lupeol (0.11%) in B. variegata and Z-guggulsterone (0.140%) and E-guggulsterone (0.146%) in purified guggul was found. The micrometrics of the powder blend of all the formulations showed good flow properties. Formulation F3 showed better results compared to other formulations in post compression evaluation. Accelerated stability study showed that the formulation F3 was stable during the course of study.Keywords
Micromeritics, Polyherbal Formulation, Polycystic Ovarian Syndrome, Physicochemical EvaluationFull Text
References
- Azeemuddin M, Anturlikar SD, Onkaramurthy M, Baig MR, Ashok BK, Rao RP, et al., Effect of “dXB2030,” a polyherbal formulation, on Experimental polycystic ovary syndrome associated with hyperandrogenism. Adv Pharmacol Sci. 2019; 2019. https://doi.org/10.1155/2019/8272850. PMid:30863446. PMCid:PMC6378078
- Patel MG, Prjapathi DP. Concept of polycystic ovarian syndrome: Perspectives of Ayurveda and Modern Science. Int J Pharmacogn Phytochem Res. 2017; 9(10):1363-72. https://doi.org/10.25258/phyto.
- v9i10.10462
- Arentz S, Abbott J, Smith C. Herbal medicine for the management of Polycystic Ovary Syndrome (PCOS). BMC Complim Altern Med. 2014; 14(2015):511-30. https://doi.org/10.1186/1472-6882-14-511.
- PMid:25524718. PMCid:PMC4528347
- Moorthy R, Prabhu KM, Murthy PS. Antihyperglycemic compound (gII) from fenugreek (Trigonella foenum-graecum linn.) seeds, its purification and effect in diabetes mellitus. Indian J Exp Biol. 2010; 48(11):1111-8.
- Renuka C, Ramesh N, Saravanan K. Evaluation of the antidiabetic effect of Trigonella foenum-graecum seed powder on alloxan-induced diabetic albino rats. Int J Pharm Tech Res. 2009; 1(4):1580-4.
- Mohammadi A, Gholamhosseinian A, Fallah H. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats. Adv Biomed Res. 2016; 5(1):54. https://doi.org/10.4103/2277-9175.178799. PMid:27110551 PMCid:PMC4817393
- Swar G, Shailajan S, Menon S. Activity based evaluation of a traditional Ayurvedic medicinal plant: Saraca asoka (Roxb.) de Wilde flowers as
- estrogenic agents using ovariectomized rat model. J Ethnopharmacol. 2017; 195:324-33. https://doi.org/10.1016/j.jep.2016.11.038. PMid:27884717
- Cibin TR, Devi DG, Abraham A. Chemoprevention of two-stage skin cancer in vivo by Saraca asoca. Integr Cancer Ther. 2012; 11(3):279-86. https://doi.org/10.1177/1534735411413264. PMid:21771821
- Jadhav AN, Bhutani KK. Ayurveda and gynecological disorders. J Ethnopharmacol. 2005; 97(1):151-9. https://doi.org/10.1016/j.jep.2004.10.020. PMid:15652289
- Shahid AP, Salini S, Sasidharan N, Padikkala J, Raghavamenon AC, Babu TD. Effect of Saraca asoka(Asoka) on estradiol-induced keratinizing metaplasia in rat uterus. J Basic Clin Physiol Pharmacol. 2015; 26(5):509-15. https://doi.org/10.1515/jbcpp-2014-0124. PMid:25915082
- Dhiman K. Ayurvedic intervention in the management of uterine fibroids: A Case series. AYU (An Int Q J Res Ayurveda). 2014; 35(3):303. https://doi.org/10.4103/0974-8520.153750. PMid:26664240.
- PMCid:PMC4649577
- Rajkapoor B, Jayakar B, Murugesh N. Antitumour activity of Bauhinia variegata on Dalton’s ascitic lymphoma. J Ethnopharmacol. 2003; 89(1):107-9. https://doi.org/10.1016/S0378-8741(03)00264-2
- S R, H. P. Alternative therapies in polycystic ovarian syndrome. Insulin. 2010; 1(2):3.
- Upwar N, Patel R, Waseem N, Mahobia NK. Hypoglycemic effect of methanolic extract of Berberis aristata DC stem on normal and streptozotocin induced diabetic rats. Int J Pharm Pharm Sci. 2011; 3(1):222-4.
- Orio F, Muscogiuri G, Palomba S, Savastano S, Volpe A, Orio M, et al., Berberine improves reproductive features in obese Caucasian women with polycystic ovary syndrome independently of changes of insulin sensitivity. ESPEN J. 2013; 8(5):e200-4. https://doi.org/10.1016/j.clnme.2013.07.002
- Razzaq FA, Khan RA, Feroz Z, Afroz S. Effect of Berberis aristata on lipid profile and coagulation parameters. African J Pharm Pharmacol. 2011;5(7):943-7.
- Sidhu GS, Mani H, Gaddipati JP, Singh AK, Seth P, Banaudha KK, et al., Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair Regen. 1999; 7(5):362-74. https://doi.org/10.1046/j.1524-475X.1999.00362.x. PMid:10564565
- Reddy PS, Begum N, Mutha S, Bakshi V. Beneficial effect of Curcumin in Letrozole induced polycystic ovary syndrome. Asian Pacific J Reprod. 2016; 5(2):116-22. https://doi.org/10.1016/j.apjr.2016.01.006
- Edition F. the Pharmacopoeia of the Pharmacopoeia of. 2016;
- on Traditional Medicine WHOP. Guidelines for the assessment of herbal medicines. World Health Organization; 1991.
- Organization WH. WHO guidelines on good manufacturing practices (GMP) for herbal medicines; 2007. p. 72.
- Khandelwal K. Practical pharmacognosy. Pragati Books Pvt. Ltd.; 2008.
- Gupta AK, Tondon N, Sharma M. Quality standards of Indian medicinal plant medicinal plants unit: Published by Indian Council of Medical Research. New Delhi. 2008;3:99-105.
- Chaube A, Dixit SK, Sharma P V. On improving the disintegration of ayurvedic pills containing guggulu. Anc Sci Life. 1995; 14(3):161-7.
- Savarikar SS, Barbhind MM, Kulkarni AP. Pharmaceutical and analytical evaluation of Triphala guggul kalpa tablets J Ayurveda Integr Med. 201; 2(1):21-25.
- Mohini U, Pallavi R, Shashikant D, Nilesh K. Assessment of guggul gum as a binding agent in tablet formulations. Res J Pharm Technol. 2013; 6(3): 238-9.
- M Hedaoo M, Patil Bhole TPB. Narrative review of guggulu formulations of ayurveda reflecting their percentage of guggulu, pharmaceutics and pharmacology. IP Int J Compr Adv Pharmacol. 2021; 5(4):151-7. https://doi.org/10.18231/j.ijcaap. 2020.031
- Khar RK. Lachman/liebermans: the theory and practice of industrial pharmacy. Cbs Publishers & Distribu; 2013.
- Aulton ME, Taylor KMG. Aulton’s pharmaceutics. Des Manuf Med. 2007; 3:176-8.
- Pharmacopoeia I. Government of India. Minist Heal Fam Welf. 2007; 2:1020-1.
- Kushwaha SK, Kori ML. Development and evaluation of polyherbal syrup from some hepatoprotective medicinal plants. 2014; 1(1):5-11.
- Balekundri A, Shahapuri A, Patil M. Poly-herbal tablet formulation by design expert tool and in vitro antilipase activity. Futur J Pharm Sci. 2020; 6(1). https://doi.org/10.1186/s43094-020-00131-0
- Maurya H, Kumar T. Formulation, standardization, and evaluation of polyherbal dispersible tablet. Int J Appl Pharm. 2019; 11(1):158-67. https://doi.org/10.22159/ijap.2019v11i1.30113
- Mamatha D. Formulation and evaluation of poly herbal anti-diabetic tablet dosage form. Int J Ayurvedic Herb Med. 2018; 6:2956-62. https://doi.org/10.18535/ijahm/v7i6.06
- Puri D, Bhandari A, Sharma K, Sharma P. Formulation and evaluation of antihelminthic polyherbal tablets. Int J Green Pharm. 2011; 5(1):39-42.
- Guideline ICHHT. Stability testing of new drug substances and products. Q1A (R2), Curr step. 2003; 4:1-24.
- The Electro-Spun Sublingual Film Containing Curcumin Micelles
Abstract Views :92 |
PDF Views:74
Authors
Affiliations
1 Department of Pharmaceutics and Pharmaceutical Technology, Parul Institute of Pharmacy, Parul University, Vadodara - 391760, Gujarat, IN
1 Department of Pharmaceutics and Pharmaceutical Technology, Parul Institute of Pharmacy, Parul University, Vadodara - 391760, Gujarat, IN
Source
Journal of Natural Remedies, Vol 23, No 1 (2023), Pagination: 205-211Abstract
Hydrophilic polymers D-tocopheryl polyethylene glycol succinate (TPGS-1000) and Poloxamer-188 were combined for the formulation of a sublingual film that aids in improving the oral bioavailability of the drug curcumin, which is not very soluble. For the formulation of micelles, the thin-film hydration technique was used and then electro-spun into a sublingual film that contained 13 % w/v PVP. Following that, prepared micelles and films were assessed and evaluated (particle size, PDI, zeta potential, %EE, pH studies, disintegration time, and in vitro drug release). According to the findings, the average particle size of the blended micelles was 230.2 nm. The ideal formulation of mixed micelles had a mean zeta potential and PDI of 20.73 mV and 0.258±0.038, respectively. Additionally, an entrapment efficiency of 82% was reached. In an aqueous medium, the film disintegrated in 40±10 seconds. Micelles were incorporated into the film without losing their integrity. Importantly, as compared to a pure drug, the films with micelles put on them showed improved bioavailability, high permeability and rapid absorption of the curcumin. Compared to the pure drug, the bioavailability of the films was increased by around 2.18 times due to the presence of mixed micelles loaded with curcumin. The results also showed that micelles-loaded sublingual films performed well in vitro for bioavailability improvement. In the end, it was found that films containing a mixture of poloxamer-188 and TPGS-1000 micelles would function effectively as carriers to boost curcumin’s bioavailability.Keywords
Electro Spinning, Micelles, Poloxamer-188, Sublingual Film, TPGS.Full Text
References
- Srimal RC. Turmeric: A brief review of medicinal properties. Fitoterapia (Milano). 1997; 68(6):483-9.
- Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: A short review. Life Sciences. 2006; 78(18):2081-7. https://doi.org/10.1016/j. lfs.2005.12.007 DOI: https://doi.org/10.1016/j.lfs.2005.12.007
- Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M. Chemopreventive and therapeutic effects of curcumin. Cancer Letters. 2005; 223(2):181-90. https://doi.org/10.1016/j.canlet.2004.09.041 DOI: https://doi.org/10.1016/j.canlet.2004.09.041
- Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Research. 2003; 23(1/A):363-98.
- Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. Retracted: Notch–1 down–regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer. 2006; 106(11):2503-13. https://doi.org/10.1002/cncr.21904 DOI: https://doi.org/10.1002/cncr.21904
- Lev-Ari S, Strier L, Kazanov D, Madar-Shapiro L, Dvory Sobol H, Pinchuk I, Marian B, Lichtenberg D, Arber N. Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clinical Cancer Research. 2005; 11(18):6738-44. https://doi.org/10.1158/1078-0432.CCR05-0171 DOI: https://doi.org/10.1158/1078-0432.CCR-05-0171
- Cruz–Correa M, Shoskes DA, Sanchez P, Zhao R, Hylind LM, Wexner SD, Giardiello FM. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clinical Gastroenterology and Hepatology. 2006; 4(8):1035-8. https://doi.org/10.1016/j. cgh.2006.03.020 DOI: https://doi.org/10.1016/j.cgh.2006.03.020
- Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK. Stability of curcumin in buffer solutions and characterization of its degradation products. Journal of Pharmaceutical and Biomedical Analysis. 1997; 15(12):1867-76. https://doi. org/10.1016/S0731-7085(96)02024-9 DOI: https://doi.org/10.1016/S0731-7085(96)02024-9
- Cheng AL, Hsu CH, Lin JK, Hsu MM, et al. “Phase I chemoprevention clinical trial of curcumin, a chemo preventive agent, in patients with high risk or pre-malignant lesions”. Anticancer Research. 2001; 21(4):2895-2900.
- Kazunori Kataoka, Atsushi Harada, Yukio Nagasaki. “Block copolymer micelles for drug delivery: design, characterization and biological significance”. Advanced Drug Delivery Reviews. 2012; 64:37-48. https://doi.org/10.1016/j. addr.2012.09.013 DOI: https://doi.org/10.1016/j.addr.2012.09.013
- Bromberg L. Polymeric micelles in oral chemotherapy. Journal of Controlled Release. 2008; 128(2):99-112. https:// doi.org/10.1016/j.jconrel.2008.01.018 DOI: https://doi.org/10.1016/j.jconrel.2008.01.018
- Attia AB, Ong ZY, Hedrick JL, Lee PP, Ee PL, Hammond PT, Yang YY. Mixed micelles self-assembled from block copolymers for drug delivery. Current Opinion in Colloid and Interface Science. 2011; 16(3):182-94. https://doi. org/10.1016/j.cocis.2010.10.003 DOI: https://doi.org/10.1016/j.cocis.2010.10.003
- Ma X, Williams RO. Polymeric nanomedicines for poorly soluble drugs in oral delivery systems: An update. Journal of Pharmaceutical Investigation. 2018; 48(1):61-75.
- Lv QY, Li XY, Shen BD, Dai L, Xu H, Shen CY, Yuan HL, Han J. A solid phospholipid-bile salts-mixed micelles based on the fast-dissolving oral films to improve the oral bioavailability of poorly water-soluble drugs. Journal of Nanoparticle Research. 2014; 16(6):1-4. https://doi. org/10.1007/s11051-014-2455-6 DOI: https://doi.org/10.1007/s11051-014-2455-6
- Guo YG, Singh AP. Emerging strategies for enhancing buccal and sublingual administration of nutraceuticals and pharmaceuticals. Journal of Drug Delivery Science and Technology. 2019; 52:440-51. https://doi.org/10.1016/j. jddst.2019.05.014 DOI: https://doi.org/10.1016/j.jddst.2019.05.014
- Hua S. Advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. Frontiers in Pharmacology. 2019; 10:1328. https://doi. org/10.3389/fphar.2019.01328 DOI: https://doi.org/10.3389/fphar.2019.01328
- Kaldybekov DB, Tonglairoum P, Opanasopit P, Khutoryanskiy VV. Mucoadhesive maleimide-functionalised liposomes for drug delivery to urinary bladder. European Journal of Pharmaceutical Sciences. 2018; 111:83- 90. https://doi.org/10.1016/j.ejps.2017.09.039 DOI: https://doi.org/10.1016/j.ejps.2017.09.039
- Ahn H, Park JH. Liposomal delivery systems for intestinal lymphatic drug transport. Biomaterials Research. 2016; 20(1):1-6. https://doi.org/10.1186/s40824-016-0083-1 DOI: https://doi.org/10.1186/s40824-016-0083-1
- Chunhachaichana C, Srichana T. Efficiency of sildenafil encapsulation in poloxamer micelles. Journal of Dispersion Science and Technology. 2019; 40(10):1461-8. https://doi. org/10.1080/01932691.2018.1518142 DOI: https://doi.org/10.1080/01932691.2018.1518142
- Wang T, Markham A, Thomas SJ, Wang N, Huang L, Clemens M, Rajagopalan N. Solution stability of poloxamer 188 under stress conditions. Journal of pharmaceutical sciences. 2019; 108(3):1264-71. https://doi.org/10.1016/j. xphs.2018.10.057 DOI: https://doi.org/10.1016/j.xphs.2018.10.057
- Tambe A, Pandita N. Enhanced solubility and drug release profile of boswellic acid using a poloxamer-based solid dispersion technique. Journal of Drug Delivery Science and Technology. 2018; 44:172-80. https://doi.org/10.1016/j. jddst.2017.11.025 DOI: https://doi.org/10.1016/j.jddst.2017.11.025
- Joseph G. Moloughney, Noah Weisleder. Poloxamer 188 (p188) as a membrane resealing reagent in biomedical applications. Recent Patents on Biotechnology. 2012; 6(3):200-11. https://doi.org/10.2174/1872208311206030200 DOI: https://doi.org/10.2174/1872208311206030200
- Singh-Joy SD, McLain VC. Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics. International Journal of Toxicology. 2008; 27:93-128. https://doi.org/10.1080/10915810802244595 DOI: https://doi.org/10.1080/10915810802244595
- Hu XY, Lou H, Hageman MJ. Preparation of lapatinib ditosylate solid dispersions using solvent rotary evaporation and hot melt extrusion for solubility and dissolution enhancement. International Journal of Pharmaceutics. 2018; 552(1-2):154-63. https://doi.org/10.1016/j. ijpharm.2018.09.062 DOI: https://doi.org/10.1016/j.ijpharm.2018.09.062
- Kim DS, Kim DW, Kim KS, Choi JS, Seo YG, Youn YS, Oh KT, Yong CS, Kim JO, Jin SG, Choi HG. Development of a novel l-sulpiride-loaded quaternary microcapsule: Effect of TPGS as an absorption enhancer on physicochemical characterization and oral bioavailability. Colloids and Surfaces B: Biointerfaces. 2016; 147:250-7. https://doi.org/10.1016/j. colsurfb.2016.08.010 DOI: https://doi.org/10.1016/j.colsurfb.2016.08.010
- Singh H, Narang JK, Singla YP, Narang RS, Mishra V. TPGS stabilized sublingual films of frovatriptan for the management of menstrual migraine: Formulation, design and antioxidant activity. Journal of Drug Delivery Science and Technology. 2017; 41:144-56. https://doi.org/10.1016/j. jddst.2017.07.008 DOI: https://doi.org/10.1016/j.jddst.2017.07.008
- Keshari P, Sonar Y, Mahajan H. Curcumin loaded TPGS micelles for nose to brain drug delivery: in vitro and in vivo studies. Materials Technology. 2019; 34(7):423-32. https:// doi.org/10.1080/10667857.2019.1575535 DOI: https://doi.org/10.1080/10667857.2019.1575535
- Jain S, Pandey S, Sola P, Pathan H, Patil R, Ray D, Aswal VK, Bahadur P, Tiwari S. Solubilization of carbamazepine in TPGS micelles: Effect of temperature and electrolyte addition. Aaps Pharm SciTech. 2019; 20(5):1-8. https://doi. org/10.1208/s12249-019-1412-1 DOI: https://doi.org/10.1208/s12249-019-1412-1
- Suksiriworapong J, Rungvimolsin T, Junyaprasert VB, Chantasart D. Development and characterization of lyophi lized diazepam-loaded polymeric micelles. Aaps Pharm SciTech. 2014; 15(1):52-64. https://doi.org/10.1208/s12249- 013-0032-4 DOI: https://doi.org/10.1208/s12249-013-0032-4
- Dai WG, Dong LC, Li S, Deng Z. Combination of Pluronic/ Vitamin E TPGS as a potential inhibitor of drug precipitation. International Journal of Pharmaceutics. 2008; 355(1-2):31- 7. https://doi.org/10.1016/j.ijpharm.2007.12.015 DOI: https://doi.org/10.1016/j.ijpharm.2007.12.015
- Nasirizadeh S, Malaekeh-Nikouei B. Solid lipid nanoparticles and nanostructured lipid carriers in oral cancer drug delivery. Journal of Drug Delivery Science and Technology. 2020; 55:101458. https://doi.org/10.1016/j. jddst.2019.101458 DOI: https://doi.org/10.1016/j.jddst.2019.101458
- Carn SA, Fioletov VE, McLinden CA, Li C, Krotkov NA. A decade of global volcanic SO2 emissions measured from space. Scientific Reports. 2017; 7(1):1-2. https://doi. org/10.1038/srep44095 DOI: https://doi.org/10.1038/srep44095
- Lim SJ, Kim CK. Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid. International Journal of Pharmaceutics. 2002; 243(1-2):135-46. https://doi. org/10.1016/S0378-5173(02)00269-7 DOI: https://doi.org/10.1016/S0378-5173(02)00269-7
- Shen CY, Yuan XD, Bai JX, Lv QY, Xu H, Dai L, Yu C, Han J, Yuan HL. Development and characterization of an orodispersible film containing drug nanoparticles. European Journal of Pharmaceutics and Biopharmaceutics. 2013; 85(3):1348-56. https://doi.org/10.1016/j.ejpb.2013.09.019 DOI: https://doi.org/10.1016/j.ejpb.2013.09.019
- Panda DS, Alruwaili NK, Pattnaik S, Swain K. Ibuprofen loaded electrospun polymeric nanofibers: A strategy to improve oral absorption. Acta Chimica Slovenica. 2022; 69(2):483-8. https://doi.org/10.17344/acsi.2022.737 DOI: https://doi.org/10.17344/acsi.2022.7370
- Sumitha CH, Varma MV, Sriniwas K. Development of taste masked fast dissolving orally consumable films of seldinafil citrate. IJPIS J Pharm Cosmet 2011; 1:1-6.
- Navamanisubramanian R, Nerella R, Chamundeeswari D,Shanmuganathan S. Use of okra mucilage and chitosan acetate in verapamil hydrochloride buccal patches development; in vitro and ex vivo characterization. J Young Pharm 2017; 9:94-9. DOI: https://doi.org/10.5530/jyp.2017.9.18