Preparation, Optimization, and Evaluation of Pellets Containing Mesalamine With Natural Gums For Colon Drug Delivery System

Yıl 2022, Cilt: 1 Sayı: 47, 35 - 56, 01.03.2022

Rijawan Rajjak Pathan Aquil-ur-rahim Sıddıquı

https://doi.org/10.55262/fabadeczacilik.1078778

Cited By: 2

Öz

The purpose of the present work was to formulate colon-targeted mesalamine pellets containing gums of Moringa oleifera Lam. (MOG) and Cyamopsis tetragonolobus Taub. (CTG). Formulation of single stimuli mediated release is also difficult to target colon due to variation in the physiological condition, so in present work, pH dependent and enzyme degradation mechanisms are being used to release of drug at the colonic site. Extrusion and spheronization techniques were used for the preparation of pellets. For formulation optimization, factorial design study 32 was used for the selection of the optimized batch. It was found that high ratio of solvent 80:20 and 10% and 7.5% concentration of MOG and CTG respectively produce optimized pellets showed good physical properties and release for F8M and F8C and after coating it showed in vitro release at the colonic condition and in vivo roentgenographic images for targeting. As to say as advantages, spheronization and extrusion method was proved to have economized, whereas natural gums used to control
release which added advantage as being as inert and biocompatible. This further formulation scope at industrial scales to reduce side effects of synthetic polymer and make it more biocompatible with the body.

Anahtar Kelimeler

Mesalamine, pellets, Moringa oleifera gum, Cyamopsis tetragonolobus gum, in vivo colon targeting

Kolona Hedefli Doğal Sakız ve Mesalamin İçeren Pelletlerin Hazırlanması, Optimizasyonu ve Değerlendirilmesi

Öz

Bu çalışmanın amacı Moringa oleifera Lam. (MOG) ve Cyamopsis tetragonolobus Taub. (CTG)’ den elde edilen sakızları içeren kolona hedefli mesalamin pelletlerinin hazırlanmasıdır. Tekli uyaran aracılı salımın kolona hedefli olarak gerçekleştirilmesinin fizyolojik koşullardan dolayı zor olması nedeniyle salımın kolonda sağlanması için pH ve enzime duyarlı salım mekanizmaları kullanılmıştır. Pelletlerin hazırlanmasında ekstrüzyon ve sferonizasyon teknikleri kullanılmıştır. Formülasyonun optimizasyonunda, optimize serinin seçimi için faktöriyel tasarım çalışması 32 kullanılmıştır. Yüksek çözücü oranı (80:20) ve MOG ve CTG’nin sırasıyla %10 ve %7.5 konsantrasyonlarda kullanımının optimize pelletlerin elde edilmesini
sağladığı saptanmıştır. Elde edilen optimize pelletler hedeflendirme için iyi fiziksel özellik göstermiş ve F8M ve F8C formülasyonları ve bunların kaplanmış formülasyonları kolon ortamında iyi in vitro salım özelliği göstermiş ve in vivo röntgenografik görüntü vermiştir. Avantaj olarak söylemek gerekirse, sferonizasyon ve ekstrüzyon ekonomik açıdan avantaj sağlarken kontrollü salım sağlamak amacıyla kullanılan doğal kaynaklı sakızlar inert ve biyouyumlu yapıları ile avantaj sağlamıştır. Bu formülasyon, endüstriyel ölçeklerde sentetik polimerin yan etkilerini azaltıp vücutla daha biyouyumlu hale getirebilir.

Anahtar Kelimeler

Mesalamin, pelletler, Moringa oleifera zamkı, Cyamopsis tetragonolobus zamkı, in vivo kolon hedefleme.

Kaynakça

• Al-Hashimi, N., Begg, N., Alany, R. G., Hassanin, H., & Elshaer, A. (2018). Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles. Pharmaceutics, 10(4), 176. Retrieved from https://doi.org/10.3390/pharmaceutics10040176
• Auriemma, G., Mencherini, T., Russo, P., Stigliani, M., Aquino, R. P., & Del Gaudio, P. (2013). Prilling for the development of multi-particulate colon drug delivery systems: Pectin vs. pectin–alginate beads. Carbohydrate Polymers, 92(1), 367–373. Retrieved from https://doi.org/10.1016/j.carbpol.2012.09.056
• Bendas, E. R., Christensen, J. M., & Ayres, J. W. (2010). Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets. Drug Development and Industrial Pharmacy, 36(4), 393–404. Retrieved from https://doi.org/10.3109/03639040903213717
• Bruschi, M. L. (2015). Mathematical models of drug release. In Strategies to Modify the Drug Release from Pharmaceutical Systems (pp. 63–86). Elsevier. Retrieved 22 March 2021 from https://doi.org/10.1016/B978-0-08-100092-2.00005-9
• Bodea, A., & Leucuta, S. E. (1997). Optimization of propranolol hydrochloride sustained release pellets using a factorial design. International Journal of Pharmaceutics, 154(1), 49–57. Retrieved from https://doi.org/10.1016/S0378-5173(97)00114-2
• Čalija, B., Cekić, N., Savić, S., Daniels, R., Marković, B., & Milić, J. (2013). pH-sensitive microparticles for oral drug delivery based on alginate/oligochitosan/Eudragit® L100-55 “sandwich” polyelectrolyte complex. Colloids and Surfaces B: Biointerfaces, 110, 395–402. Retrieved from https://doi.org/10.1016/j.colsurfb.2013.05.016
• Cao, Q., Jin, L., Ding, Y., Zhang, Y., & Xu, X. (2016). A novel pH–enzyme-dependent mesalamine colon-specific delivery system. Drug Design, Development and Therapy, 2021. Retrieved from https://doi.org/10.2147/DDDT.S107283
• Costa, F. O., Sousa, J. J. S., Pais, A. A. C. C., & Formosinho, S. J. (2003). Comparison of dissolution profiles of Ibuprofen pellets. Journal of Controlled Release, 89(2), 199–212. Retrieved from https://doi.org/10.1016/S0168-3659(03)00033-6
• Deshpande, R. D., Gowda, D. V., & Mahammed, N. (2013). Design of Pistacia lentiscus (mastic gum) controlled release spheroids and investigating the influence of roll compaction. Industrial Crops and Products, 44, 603–610. Retrieved from https://doi.org/10.1016/j.indcrop.2012.09.014
• Dubernet, C., Benoit, J. P., Peppas, N. A., & Puisieux, F. (1990). Ibuprofen-loaded ethylcellulose microspheres: Release studies and analysis of the matrix structure through the Higuchi model. Journal of Microencapsulation, 7(4), 555–565. Retrieved from https://doi.org/10.3109/02652049009040479
• Eriksson, M., Alderborn, G., Nyström, C., Podczeck, F., & Newton, J. M. (1997). Comparison between and evaluation of some methods for the assessment of the sphericity of pellets. International Journal of Pharmaceutics, 148(2), 149–154. Retrieved from https://doi.org/10.1016/S0378-5173(96)04845-4
• Friciu, M. M., Le, T. C., Ispas-Szabo, P., & Mateescu, M. A.(2013). Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic mesalamine forms for colon delivery. European Journal of Pharmaceutics and Biopharmaceutics 85(3), 521–530. Retrieved from https://doi.org/10.1016/j.ejpb.2013.03.007
• Hamedelniel, E. I., Bajdik, J., & Pintye-Hódi, K. (2010). Optimization of preparation of matrix pellets containing ethylcellulose. Chemical Engineering and Processing: Process Intensification, 49(1), 120–124. Retrieved from https://doi. org/10.1016/j.cep.2009.12.002
• Hanauer, S. B. (1998). Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute ulcerative proctosigmoiditis: Results of a multicentered placebo-controlled trial. Inflammatory Bowel Diseases, 4(2), 79–83.
• Hanauer, S., Schwartz, J., Robinson, M., Roufail, W., Arora, S., Cello, J., & Safdi, M. (1993). Mesalamine capsules for treatment of active ulcerative colitis: Results of a controlled trial. American Journal of Gastroenterology (Springer Nature), 88(8).
• Hedin, C., Whelan, K., & Lindsay, J. O. (2007). Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proceedings of the Nutrition Society, 66(3), 307–315. Retrieved from https://doi.org/10.1017/S0029665107005563
• Hileman, G. A., Goskonda, S. R., Spalitto, A. J., & Upadrashta, S. M. (1993). Response surface optimization of high dose pellets by extrusion and spheronization. International Journal of Pharmaceutics, 100(1–3), 71–79. Retrieved from https://doi.org/10.1016/0378-5173(93)90077-S
• Ige, P. P., & Gattani, S. G. (2012). Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: A technical note. Archives of Pharmacal Research, 35(3), 487–498. Retrieved from https://doi.org/10.1007/s12272-012-0312-7
• Isaac, G. S. (2018). In Pellets: a general overview, Pharmaceutical Pelletization Technology. informa health care, New York, London
• Joshi, A., Pund, S., Nivsarkar, M., Vasu, K., & Shishoo, C. (2008). Dissolution test for site-specific release isoniazid pellets in USP apparatus 3 (reciprocating cylinder): Optimization using response surface methodology. European Journal of Pharmaceutics and Biopharmaceutics, 69(2), 769–775. Retrieved from https://doi.org/10.1016/j.ejpb.2007.11.020
• Kaffash, E., Saremnejad, F., Abbaspour, M., Mohajeri, S. A., Garekani, H. A., Jafarian, A. H., … Nokhodchi, A. (2019). Statistical optimization of alginate-based oral dosage form of 5-aminosalicylic acid aimed to colonic delivery: In vitro and in vivo evaluation. Journal of Drug Delivery Science and Technology, 52, 177–188. Retrieved from https://doi.org/10.1016/j.jddst.2019.04.006
• Kakar, S., Batra, D., & Singh, R. (2013). Preparation and evaluation of magnetic microspheres of mesalamine (5-aminosalicylic acid) for colon drug delivery. Journal of Acute Disease, 2(3), 226–231. Retrieved from https://doi.org/10.1016/S2221-6189(13)60132-8
• Kam, L., Cohen, H., Dooley, C., Rubin, P., & Orchard, J. (1996). A comparison of mesalamine suspension enema and oral sulfasalazine for treatment of active distal ulcerative colitis in adults. American Journal of Gastroenterology (Springer Nature), 91(7).
• Korsmeyer, R. W., Gurny, R., Doelker, E., Buri, P., &Peppas, N. A. (1983). Mechanisms of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics, 15(1), 25–35.Retrieved from https://doi.org/10.1016/0378-5173(83)90064-9
• Liu, L., Fishman, M. L., Kost, J., & Hicks, K. B. (2003). Pectin-based systems for colon-specific drug delivery via oral route. Biomaterials, 24(19), 3333– 3343. Retrieved from https://doi.org/10.1016/S0142-9612(03)00213-8
• Lorenzo-Lamosa, M. L., Remuñán-López, C., Vila-Jato, J. L., & Alonso, M. J. (1998). Design of microencapsulated chitosan microspheres for colonic drug delivery. Journal of Controlled Release, 52(1–2), 109–118. Retrieved from https://doi.org/10.1016/S0168-3659(97)00203-4
• Mezreb, N., Charrueau, C., Boy, P., Allain, P., & Chaumeil, J. C. (2004). Production of Carbopol®974P and Carbopol® 971P Pellets by Extrusion‐Spheronization: Optimization of the Processing Parameters and Water Content. Drug Development and Industrial Pharmacy, 30(5), 481–490. Retrieved from https://doi.org/10.1081/DDC-120037476
• Mohanta, S., Singh, S. K., Kumar, B., Gulati, M., Kumar, R., Yadav, A. K., … Pandey, N. K. (2019). Efficacy of co-administration of modified apple polysaccharide and probiotics in guar gum-Eudragit S100 based mesalamine mini tablets: A novel approach in treating ulcerative colitis. International Journal of Biological Macromolecules, 126, 427–435. Retrieved from https://doi.org/10.1016/j.ijbiomac.2018.12.154
• Muley, S., Nandgude, T., & Poddar, S. (2016). Extrusion–spheronization a promising pelletization technique: In-depth review. Asian Journal of Pharmaceutical Sciences, 11(6), 684–699. Retrieved from https://doi.org/10.1016/j.ajps.2016.08.001
• Muley, S. S., Nandgude, T., & Poddar, S. (2017). Formulation and Optimization of Lansoprazole Pellets Using Factorial Design Prepared by Extrusion-Spheronization Technique Using Carboxymethyl Tamarind Kernel Powder. Recent Patents on Drug Delivery & Formulation, 11(1). Retrieved 9 February 2021 from https://doi.org/10.2174/1872211311666170113150248
• Parmar, C., Parikh, K., Mundada, P., Bhavsar, D., & Sawant, K. (2018). Formulation and optimization of enteric coated bilayer tablets of mesalamine by RSM: In vitro – In vivo investigations and roentogenographic study. Journal of Drug Delivery Science and Technology, 44, 388–398. Retrieved fromhttps://doi.org/10.1016/j.jddst.2018.01.008
• Patel, M. M., & Amin, A. F. (2011). Process, optimization and characterization of mebeverine hydrochloride loaded guar gum microspheres for irritable bowel syndrome. Carbohydrate Polymers, 86(2), 536–545. Retrieved from https://doi.org/10.1016/j.carbpol.2011.04.068
• Patel, M. M., Shah, T. J., Amin, A. F., & Shah, N. N. (2009). Design, Development and Optimization of a Novel Time and pH-Dependent Colon Targeted Drug Delivery System. Pharmaceutical Development and Technology, 14(1), 65–72. Retrieved from https://doi.org/10.1080/10837450802409412
• Paterakis, P. G., Korakianiti, E. S., Dallas, P. P., & Rekkas, D. M. (2002). Evaluation and simultaneous optimization of some pellets characteristics using a 33 factorial design and the desirability function. International Journal of Pharmaceutics, 248(1–2), 51–60. Retrieved from https://doi.org/10.1016/S0378-5173(02)00341-1
• Pawar, P. K., & Gautam, C. (2016). Design, optimization and evaluation of mesalamine matrix tablet for colon drug delivery system. Journal of Pharmaceutical Investigation, 46(1), 67–78. Retrieved from https://doi.org/10.1007/s40005-015-0214-z
• Podczeck, F., Rahman, S. R., & Newton, J. M. (1999). Evaluation of a standardised procedure to assess the shape of pellets using image analysis. International Journal of Pharmaceutics, 192(2), 123–138. Retrieved from https://doi.org/10.1016/S0378
• Pund, S., Joshi, A., Vasu, K., Nivsarkar, M., & Shishoo, C. (2010). Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets. International Journal of Pharmaceutics, 388(1–2), 64–72. Retrieved from https://doi.org/10.1016/j.ijpharm.2009.12.034
• Quinteros, D. A., Manzo, R. H., & Allemandi, D. A. (2010). Design of a colonic delivery system based on cationic polymethacrylate (EudragitE100)-mesalamine complexes. Drug Delivery, 17(4), 208–213. Retrieved from https://doi.org/10.3109/10717541003667806
• Safdi, M., DeMicco, M., Sninsky, C., Banks, P., Wruble,L., Deren, J., … Fleishman, C. (1997). A Double–Blind Comparison of Oral versus Rectal mesalamine versus Combination Therapy in the Treatment of Distal Ulcerative Colitis. American Journal of Gastroenterology (Springer Nature), 92(10).
• Santos, H., Veiga, F., Pina, M. E., & Sousa, J. J. (2004). Compaction, compression and drug release characteristics of xanthan gum pellets of different compositions. European Journal of Pharmaceutical Sciences, 21(2–3), 271–281. Retrieved from https://doi.org/10.1016/j.ejps.2003.10.016
• Seifirad, S., Karami, H., Shahsavari, S., Mirabbasi, F.,& Dorkoosh, F. A. (2016). Design and Characterization of Mesalamine Loaded Nanoparticles for Controlled Delivery System, 10.
• Shaikh, M. S., & Kale, M. A. (2020). Formulation and molecular docking simulation study of luliconazole nanosuspension–based nanogel for transdermal drug delivery using modified polymer. Materials Today Chemistry, 18, 100364. Retrieved from https://doi.org/10.1016/j.mtchem.2020.100364
• Singh, A. K., & Pathak, K. (2015). Colon specific CODES based Piroxicam tablet for colon targeting: statistical optimization, in vivo roentgenography and stabilityassessment. Pharmaceutical Development and Technology, 20(2), 237–245. Retrieved from https://doi.org/10.3109/10837450.2013.860549
• Singh, B., & Kumar, A. (2018a). Hydrogel formation by radiation induced crosslinked copolymerization of acrylamide onto moringa gum for use in drug delivery applications. Carbohydrate Polymers, 200, 262–270. Retrieved from https://doi.org/10.1016/j.carbpol.2018.08.018
• Singh, B., & Kumar, A. (2018b). Network formation of Moringa oleifera gum by radiation induced crosslinking: Evaluation of drug delivery, network parameters and biomedical properties. International Journal of Biological Macromolecules, 108, 477–488. Retrieved from https://doi.org/10.1016/j.ijbiomac.2017.12.041
• Singh, S. K., Reddy, I. K., & Khan, M. A. (1996). Optimization and characterization of controlled release pellets coated with an experimental latex:II. Cationic drug. International Journal of Pharmaceutics, 141(1–2), 179–195. Retrieved from https://doi.org/10.1016/0378-5173(96)04635-2
• Singhal, A., Daud, A., Jarald, E., & Showkat, A. (2012). In vitro evaluation of Moringa oleifera gum for colon-specific drug delivery. International Journal of Pharmaceutical Investigation, 2(1), 48. Retrieved from https://doi.org/10.4103/2230-973X.96926
• Sinha, V. R., & Kumria, R. (2001a). Polysaccharides in colon-specific drug delivery. International Journal of Pharmaceutics, 224(1–2), 19–38. Retrieved from https://doi.org/10.1016/S0378-5173(01)00720-7
• Sinha, V.R., & Kumria, R. (2001b). Colonic drug delivery: prodrug approach. Pharm Res,18(5), 557-64. https://doi.org/10.1023/a:1011033121528
• Stolk, L. M. L., Rietbroek, R., Wiltink, E. H., & Tukker,J. J. (1990). Dissolution profiles of mesalazine formulationsin vitro. Pharmaceutisch Weekblad Scientific Edition, 12(5), 200–204. Retrieved from https://doi.org/10.1007/BF01980047
• Tho, I., Sande, S. A., & Kleinebudde, P. (2002). Pectinic acid, a novel excipient for production of pellets by extrusion/spheronisation: preliminary studies. European Journal of Pharmaceutics and Biopharmaceutics, 54(1), 95–99. Retrieved from https://doi.org/10.1016/S0939-6411(02)00048-6
• Tiwari, A., Verma, A., Panda, P. K., Saraf, S., Jain, A.,& Jain, S. K. (2019). Stimuli-responsive polysaccharides for colon-targeted drug delivery. In Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications (pp. 547–566). Elsevier. Retrieved 29 May 2021 from https://doi.org/10.1016/B978-0-08-101995-5.00022-2
• Tiwari, A., & Prabaharan, M. (2010). An Amphiphilic Nanocarrier Based on Guar Gum-graft-Poly(ε-caprolactone) for Potential Drug-Delivery Applications.Journal of Biomaterials Science, Polymer Edition, 21(6–7), 937–949. Retrieved from https://doi.org/10.1163/156856209X452278
• Tuğcu-Demiröz, F., Acartürk, F., Takka, S., &Konuş-Boyunağa, Ö. (2004). In-vitro and In-vivo Evaluation of Mesalazine–Guar Gum Matrix Tablets for Colonic Drug Delivery. Journal of Drug Targeting, 12(2), 105–112. Retrieved from https://doi.org/10.1080/10611860410001693751
• Tuğcu-Demiröz, F., Acartürk, F., Takka, S., & Konuş-Boyunağa, Ö. (2007). Evaluation of alginate based mesalazine tablets for intestinal drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 67(2), 491–497. Retrieved from https://doi.org/10.1016/j.ejpb.2007.03.003