Formulation and evaluation of orally dispersible tablets of Chlorpheniramine Maleate by fusion method

Year 2017, Volume: 21 Issue: 1, 67 - 77, 20.09.2016

Vivek Dave Renu Bala Yadav Richa Ahuja Atul Kumar Sahu

https://doi.org/10.12991/marupj.259883

Abstract

Many conventional dosage form comes in market to achieve their therapeutic value as it administered through the given route. But sometimes People feel trouble in swallowing of conventional dosage forms like tablet and capsule without taking water or due to lack availability of water during long journey.  In these cases, rapidly disintegrating tablets in oral cavity are paid attention nowadays. These are known as orally dispersible tablets which disintegrate in mouth as put on tongue resulting in release of drug which dissolve and disperse in saliva. Drug rapidly converts into solution from solid form resulting in rapid absorption and onset of action. After formulation, evaluation of these tablets were done such as weight variation, hardness, friability, disintegration, drug-polymer interaction, FTIR studies, SEM studies, water content, drug content, water absorption ratio, wetting time and in-vitro drug release and short term stability studies. These tablets (all formulations that is F1-F10) showed weight variation in range of 253± 0.05 to 291± 0.61 mg, hardness of 2.1± 0.1 to 3.5± 0.07 Kg/cm², friability of 0.44±0.01 to 0.69±0.01%, disintegration time of 20± 0.08 to 34±1.1 seconds, drug content of 92.0 to 99.18%, water absorption ratio of 26±1.12 to 49 ± 3.01 %, wetting time of 53± 1.89 to 104± 4.89 sec and in-vitro drug release showed 85.66 to 99.88% within 5 minutes. FTIR studies showed that there is no interaction between drug and polymer. Stability studies showed that there is no change in drug release upon storage on different temperature and humidity. Results revealed that orally dispersible tablets of Chlorpheniramine maleate prepared by fusion method result in rapid dissolution.  

Keywords

Chlorpheniramine maleate, Fusion method, FTIR, SEM, Full factorial design

Füzyon Yöntemiyle hazırlanan klorfeniramin maleat içeren ağızda dağılan tabletlerin formülasyonu ve değerlendirilmesi

Abstract

Ticari ürün olarak klinik
kullanıma sunulan birçok ilaç veriliş  yolunma
bağlı olarak terapötik değer kazanmaktadır. İnsanlar  tablet ve kapsül gibi konvansiyonel dozaj
formlarını, yolculuk  gibi nedenlerle su
bulamadıkları zamanlarda yutmakta  zorlanmaktadırlar.
Bu gibi durumlarda kullanılmak üzere  ağız
boşluğunda hızla dağılan tabletler dikkati çekmektedir.  Ağızda dağılan tabletler, dil üzerine
yerleştirildiğinde dozaj  formu tükürük
vasıtasıyla dağılmakta ve ilaç çözünmektedir. 
Katı formdaki ilaç hızla çözeltiye dönüşmekte ve bu durum  ilacın emilimini ve etkinin başlamasını hızlandırmaktadır.  Formülasyonlar hazırlandıktan sonra elde
edilen tabletler;  ortalama tablet
ağırlığı ve ağırlık tekdüzeliği, sertlik, ufalanmaaşınma,  dağılma zamanı, ilaç-polimer etkileşimleri,
etken  madde içeriği, su emme oranı,
in-vitro ilaç salım özellikleri  ve kısa
süreli stabilite özellikleri açısından değerlendirilmiş,  FTIR çalışmaları ve SEM çalışmaları
yapılmıştır. F1-F10 olarak  isimlendirilen
tüm formülasyonların ortalama tablet ağırlığı 
ve ağırlık tekdüzeliği 253± 0.05 - 291± 0.61 mg, sertliği 2.1±  0.1 - 3.5± 0.07 Kg/cm², ufalanma-aşınma
yüzdesi % 0.44±0.01  - 0.69±0.01, dağılma
zamanı 20± 0.08 - 34±1.1 saniye, etken  madde
içeriği % 92.0 - 99.18, su emme oranı 26±1.12 - 49 ±  3.01, ıslanma zamanı 53± 1.89 - 104± 4.89
saniye ve 5 dakika  içerisinde in-vitro
ilaç salım yüzdesi % 85.66 -99.88 olarak 
belirlenmiştir. FTIR çalışmaları, ilaç ve polimer arasında bir  etkileşim olmadığını göstermiştir. Stabilite
çalışmaları ilacın  farklı sıcaklık ve
nem ortamında saklandığında ilaç salım  özelliğinin
değişmediğini göstermiştir. Elde edilen sonuçlar  füzyon yöntemiyle hazırlanan ve klorfeniramin
maleat içeren  ağızda dağılan tabletlerin
hızlı dissolüsyona uğradığını  göstermiştir.  

Keywords

Klorfeniarmin maleat, füzyon yöntemi, FTIR, SEM, Tam Faktöriyel Tasarım

References

• Douroumis DD, Gryczke A, Schminke S. Development and evaluation of cetirizine HCl taste-masked oral disintegrating tablets. AAPS PharmSciTech. 2011; 12(1): 141-51.
• Martino PD, Martelli S, Wehrlé P. Evaluation of different fast melting disintegrants by means of a central composite design. Drug Dev Ind Pharm. 2005; 31(1): 109-21.
• Haware RV, Chaudhari PD, Parakh SR, Bauer-Brandl A. Development of a melting tablet containing promethazine HCl against motion sickness. AAPS PharmSciTech 2008; 9(3): 1006-15.
• Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique, AAPS PharmSciTech 2006; 7. Article 68; DOI: 10.1208/pt070368.
• Gupta V, Gupta M, Madan AK. Development of modified dosage form for enhancement of dissolution rate through amalgamation of solid dispersion and cube sugar or sintering technology using famotidine as a model drug. J Pharm Sci Technol 2009; 63(1):58-70.
• Ahmed IS, Nafadi MM, Fatahalla FA. Formulation of a fast-dissolving ketoprofen tablet using freeze-drying in blisters technique. Drug Dev Ind Pharm. 2006; 32(4): 437-42.
• Sarfraz RM, Khan HU, Mahmood A, Ahmad M, Maheen S, Sher M. Formulation and evaluation of mouth disintegrating tablets of atenolol and atorvastatin. Indian J Pharm Sci 2015; 77(1): 83-90.
• Seager H. Drug delivery Products and the Zydis fast dissolving dosage forms. J Pharm Pharmacol 1998; 58: 375–382.
• Mizumoto T, Masuda Y, Kajiyama A., Yanagisawa M., Nyshadham JR., Tablets quickly disintegrating in the oral cavity and process for producing the same. 2003, US Patent 6,589,554.
• Shah PP, Mashru RC. Development and Evaluation of Artemether Taste Masked Rapid Disintegrating Tablets with Improved Dissolution Using Solid Dispersion Technique 2009; 9: 494-500.
• Giri TK, Tripathi DK, Majumdar R. Formulation aspects in the development of Orodispersible tablets: An Overview. IJPPS 2010; 2(3): 38-42.
• Philippe C. Coated granules based on angiotensin-converting enzyme inhibitor. 2001, US Patent 20040171669.
• Lakshmi CSR, Sagar PA, Anup VT, Chaudhary JJ, Nitesh JP, Vedhavati SV. Development and characterization of melt in mouth tablets of atenolol by sublimation technique. Int J Pharm Res Dev 2011; 3(3): 27-36.
• Kalia A, Khurana S, Bedi N. Formulation and evaluation of mouth dissolving tablets of oxcarbazepine. Int J Pharm Sci 2009; 1(1): 12-23.
• Pahwa R, Piplani M, Garg VK, Rao R, Lamba HS. Formulation and evaluation of orally disintegrating tablets: comparison of natural and synthetic superdisintegrants. Der Pharmacia Lettre 2011; 3 (2): 407-18.
• Yunxia B, Sunada H, Yonezawa Y, Danzok K. Evaluation of rapid disintegration tablets prepared by direct compression method. Drug Dev Ind Pharm 1999: 25 (5): 571-581.
• Gopal VS, Averineni RK, Yogendra NU, Karktik A, Ranjan OP, Ginjupalli K, Pandey S, Udupa N. Enhanced dissolution and bioavailability of Gliclazide using solid dispersion techniques. Int J Drug Dev 2010; 2(1): 49-57.
• Upendra K, Raghavendra NG. Design and development of aceclofenac fast dissolving tablets by amorphous solid dispersion technique using modified aegle marmelos gum. Int J Pharm Res Dev 2011; 3(6): 201-10.
• Rajitha K, Shravan YK, Adukondalu D, Ramesh G, Rao YM. Formulation and evaluation of orally disintegrating tablets of buspirone. Int J Pharm Sci Nanotech 2009; 1(4): 327-334.
• Raju SA, Rampure MV, Shrisand SB, Swamy PV, Nagendra DK, Baswaraj B, Raghunandan D. Formulation and evaluation of orodispersible tablets of alfuzosin. Int J Pharm Tech Res 2010; 2(1): 84-88.
• Yuan CS, Karrison T, Wu JA, Lowell TK, Lynch JP, Foss JF. Dose-related effects of oral acetaminophen on cold-induced pain: a double-blind, randomized, placebo-controlled trial. Clin Pharmacol Ther 1998; 63 (3): 379–383.
• Prescott LF. Mechanism and site of absorption. In: Paracetamol (Acetaminophen): A Critical Bibliographic Review. Taylor and Francis, London, U.K. 2003; 33–66.
• Danjo K, Kozaki K, Sunada H, Otsuka A. Influence of the molecular weight of binding agents on the physical properties of granules and tablets. Chem Pharm Bull 1994; 42(10): 2121-2125.
• Devi NK, Rani AP, Mrudula BS. Formulation and evaluation of oral disintegrating tablets of montelukast sodium, effect of functionality of superdisintegrants. J Pharma Res 2010; 3(4): 803-808.
• Gandhi CK, Patel MR, Patel KR, Patel NM. A review: Taste masking in pharmaceuticals. Int J Pharm Res Dev 2011; 3(3): 19 -26.
• Bala R, Sharma S, Sharma N, Gupta DG. Development of non-bitter zolpidem tartrate mouth dissolving tablet. J Pharm Res 2009; 2(9): 1530-1535.
• Mukesh P, Ratnaparkhi, Mohanta GP, Upadhyay L. Review on: Fast dissolving tablet. J Pharm Res 2009; 2(1): 5-12.
• Kaith BS, Sharma R, Kalia S, Bhatti MS. Response surface methodology and optimized synthesis of guar gum-based hydrogels with enhanced swelling capacity. RSC Adv 2014; 4: 40339-40344. doi:10.1039/C4RA05300A
• Steinberg DM, Kenett RS. Response surface methodology. Wiley StatsRef: Statistics Reference Online. 2014; doi: 10.1002/9781118445112.stat04105.
• Kharb V, Saharan VA, Dev K, Jadhav H, Purohit S. formulation, evaluation and 3(2) full factorial design-based optimization of ondansetron hydrochloride incorporated taste masked microsphere. Pharm Dev Tech 2014; 19(7): 839-852 doi: 10.3109/10837450.2013.836220.
• Dave BS, Amin AF, Patel MM. Gastroretentive drug delivery system of ranitidine hydrochloride: formulation and in vitro evaluation. AAPS Pharm Sci Tech 2014; 5(2):1–6. doi: 10.1208/pt050234.
• Trapani A, Laquintana V, Denora N, Lopedota A, Cutrignelli A, Franco M, Trapani G, Liso G. Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies. Eur J Pharm Sci 2007; 30(1): 64–74. doi: 10.1016/j.ejps.2006.10.003
• Bi Y, Sunada H, Yonezawa Y. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull 1996; 44: 212-17
• Nogami H, Nagai T, Fukuoka E, Sonobe T. Disintegration of the aspirin tablets containing potato starch and microcrystalline cellulose in various concentrations. Chem Pharm Bull 1969;17:1450-5
• Kornblum SS, Stoopak SB. A new tablet disintegrating agent: cross-linked polyvinylpyrrolidone. J Pharm Sci 1973; 62: 43-9
• Shah U, Augsburge L. Evaluation of the functional equivalence of crospovidone NF from different sources. II. Standard performance test. Pharm Dev Technol. 2001; 6: 419-30
• Franse´n N, Morin M, Bjӧrk E, Edsman K. Physicochemical interactions between drugs and superdisintegrants. J Pharm Pharmacol. 2008; 60: 1583-9
• Soh JL, Grachet M, Whitlock M, Lukas T. Characterization, optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets. Pharm Dev Technol. 2013; 18: 172-85
• Thompson JA, Shioshita GW. Influence of substrate configuration on chlorpheniramine N-demethylation by hepatic microsomes from rats, rabbits, and mice. Drug Meta Disp 1981; 9(1): 5-9.
• Babar A, Ray SD, Patel NK, Plakogiannis FM, Gogineni P. In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin. Drug Dev Ind Pharm 1999; 25 (2): 235-240.
• Velissaratou AS, Papaioannou G. In vitro release of chlorpheniramine maleate from oinment bases. Int J Pharm 1989; 52: 83-86.
• Babar A, Bhandari RD, Plakogiannis PM. In vitro release studies of chlorpheniramine maleate from topical bases using cellulose membrane and hairless mouse skin. Drug Dev Ind Pharm 1991; 17 (8): 1027-1040.
• Nagar P, Singh K, Chauhan I, Verma M, Yasir AK, Sharma R, Gupta N. Orally disintegrating tablets: formulation, preparation techniques and evaluation. J App Pharm Sci 2011; 01: 35-45.
• Sharma D, Kumar D, Singh M, Singh G, Rathore MS. Fast Disintegrating Tablets: A New Era in novel drug delivery system and new market opportunities. J Drug Del Ther 2012; 2: 74-86.
• Hirani JJ, Rathod DA, Vadalia KR. Orally disintegrating tablets: a review. Trop J Pharm Res 2009; 8: 161-172.
• Abay FB, Ugurlu T. Orally disintegrating tablets: a short review. J Pharm Drug Dev 2015; 3: 1-8.
• Arora P, Sethi VA. Orodispersible tablets: a comprehensive review. Int J Res Dev Pharm Sci. 2013; 2: 270-284.
• Hao L, Min L, Wen Q, Zheyi H, Ed B, James J, Hassan A. Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics. Drug Dev Ind Pharm Early Online: 1-9.
• Fu Y, Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies. Crit Rev Ther Drug Carrier Syst 2004; 21(6): 433-475.