Design and Development of a Microwave Generated Lactose Monohydrate - Microcrystalline Cellulose Based Multifunctional Excipient Composites for Tablet Formulation using Box–Behnken Design

  • Sachin Shivaji Kushare Research Scholar, School of Pharmacy, Swami Ramanand Teerth Marathwada University,
  • S. G. Gattani Professor, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri Nanded, (M.S.) India. Pin – 431606

Abstract

The concept of co-processing as a particle engineering technique continues to be used as a tool to enhance the functionality of several existing excipients. This important research was designed to improve the functionality of lactose monohydrate as excipient for direct compression by co-processing with microcrystalline cellulose. Microwave induced diffusion technique was first utilized for manufacturing Co processed lactose monohydrate (LM) - microcrystalline cellulose (MC) composites. The objective of the research was to obtain synergistic effects, incorporating better tablet adherence and hardness capacity. Box-Behnken experimental design was worked out to optimize the proportion of the primary excipients for the co-processed excipient. Fifteen experiments were carried out to assess the effect of primary excipients and mixing time required to prepare a slurry for microwaving treatment on percent fines, angle of repose, Carr’s index, friability, tensile strength, disintegration time as responses. The combination of the co-processed excipient that constructed significant characteristics after optimization was observed to be 70 % alpha-Lactose-monohydrate and 30 % microcrystalline cellulose. Consequently, Microcrystalline Cellulose-Lactose composites (MCLM), a co-processed excipient, was developed that offers functionality for direct compression, as a result of given flowability and compactability. Solid-state characterization was performed on optimized composites to ascertain its particle size, shape, distribution, surface morphology, degree of crystallinity, hygroscopicity, compatibility etc. employing proven analytical methods. Powder characteristics were determined by bulk and tapped densities, angle of repose, porosity, lubricant sensitivity ratio, dilution potential etc. The compaction patterns of MCLM were assessed employing Heckel and Kawakita equations and the compressibility, tabletability, compactability (CTC) profile was determined compared to the physical mixture of the native excipients and Cellactose. Tablets were developed by direct compression using paracetamol as the drug of choice. The results imply that microwave generated MCLM composites offers improved properties in comparison with native MC and LM. The current study highlights the concept of microwave drying technique as a cost-effective means for manufacturing multifunctional directly compressible excipient in comparison to the spray-drying technique.

Downloads

Download data is not yet available.

Author Biography

S. G. Gattani, Professor, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri Nanded, (M.S.) India. Pin – 431606

Professor, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri Nanded, (M.S.) India. Pin – 431606

References

1. Sam, A. and J. Fokkens, The drug delivery system: adding therapeutic and economic value to pharmacotherapy, Part II. Pharmaceutical Technology Europe, 1997. 9: p. 58-67.
2. Rasenack, N. and B.W. Müller, Crystal habit and tableting behavior. International journal of pharmaceutics, 2002. 244(1-2): p. 45-57.
3. Shangraw, R.F., Compressed tablets by direct compression. Pharmaceutical dosage forms: Tablets, 1989. 1: p. 195-246.
4. Khan, K.A. and C.T. Rhodes, Production of tablets by direct compression. Canadian Journal of Pharmaceutical Sciences, 1973. 8(1): p. 1-5.
5. Swarbrick, J., Encyclopedia of pharmaceutical technology. 2013: CRC Press.
6. Allen, L. and H.C. Ansel, Ansel's pharmaceutical dosage forms and drug delivery systems. 2013: Lippincott Williams & Wilkins.
7. Rojas, J., Y. Ciro, and L. Correa, Functionality of chitin as a direct compression excipient: An acetaminophen comparative study. Carbohydrate polymers, 2014. 103: p. 134-139.
8. Echeverri Pineda, E.M., Producción, caracterización y propiedades funcionales de un nuevo excipiente coprocesado a partir de sorbitol y fosfato de calcio anhidro. 2015.
9. Rojas, J., Excipient design by co-processing for direct compression applications, in Excipient Applications in Formulation Design and Drug Delivery. 2015, Springer. p. 589-612.
10. Jacob, S., et al., Novel co-processed excipients of mannitol and microcrystalline cellulose for preparing fast dissolving tablets of glipizide. Indian Journal of Pharmaceutical Sciences, 2007. 69(5): p. 633.
11. Nachaegari, S.K. and A.K. Bansal, Coprocessed excipients for solid dosage forms. Pharmaceutical technology, 2004. 28(1): p. 52-65.
12. Saha, S. and A.F. Shahiwala, Multifunctional coprocessed excipients for improved tabletting performance. Expert opinion on drug delivery, 2009. 6(2): p. 197-208.
13. Rojas, J., I. Buckner, and V. Kumar, Co-proccessed excipients with enhanced direct compression functionality for improved tableting performance. Drug development and industrial pharmacy, 2012. 38(10): p. 1159-1170.
14. Wang, S., et al., Novel coprocessed excipients composed of lactose, HPMC, and PVPP for tableting and its application. International journal of pharmaceutics, 2015. 486(1-2): p. 370-379.
15. Chauhan, S.I., et al., Development and characterization of multifunctional directly compressible co-processed excipient by spray drying method. AAPS PharmSciTech, 2017. 18(4): p. 1293-1301.
16. Sharma, P., S.R. Modi, and A.K. Bansal, Co-processing of hydroxypropyl methylcellulose (HPMC) for improved aqueous dispersibility. International journal of pharmaceutics, 2015. 485(1-2): p. 348-356.
17. Olowosulu, A., et al., Formulation and evaluation of novel coprocessed excipients of maize starch and acacia gum (StarAc) for direct compression tabletting. International Journal of Pharmaceutical Research and Innovation, 2011. 2: p. 39-45.
18. Mshelia, J., Y. Apeji, and O. Olayemi, Powder, compaction and tableting properties of co-processed silicified starch. Methodology, 2013.
19. Goyanes, A., C. Souto, and R. Martínez-Pacheco, Co-processed MCC-Eudragit® E excipients for extrusion–spheronization. European Journal of Pharmaceutics and Biopharmaceutics, 2011. 79(3): p. 658-663.
20. Kittipongpatana, O.S. and N. Kittipongpatana, Preparation and physicomechanical properties of co-precipitated rice starch-colloidal silicon dioxide. Powder technology, 2012. 217: p. 377-382.
21. Adeoye, O. and G. Alebiowu, Flow, packing and compaction properties of novel coprocessed multifunctional directly compressible excipients prepared from tapioca starch and mannitol. Pharmaceutical development and technology, 2014. 19(8): p. 901-910.
22. Katsuno, E., et al., Orally disintegrating tablets prepared by a co-processed mixture of micronized crospovidone and mannitol using a ball mill to improve compactibility and tablet stability. Powder technology, 2013. 241: p. 60-66.
23. Daraghmeh, N., et al., Preparation and characterization of a novel co-processed excipient of chitin and crystalline mannitol. AAPS pharmscitech, 2010. 11(4): p. 1558-1571.
24. Vanhoorne, V., et al., Crystal coating via spray drying to improve powder tabletability. European Journal of Pharmaceutics and Biopharmaceutics, 2014. 88(3): p. 939-944.
25. Sreekanth Babu, S., A. Ajay Kumar, and D. Suman, Co-processed excipients: a review. International journal of current trends in pharmaceutical research, 2013. 1(3): p. 205-214.
26. Thoorens, G., et al., Microcrystalline cellulose, a direct compression binder in a quality by design environment—A review. International Journal of Pharmaceutics, 2014. 473(1-2): p. 64-72.
27. Akram, M., S.B.S. Naqvi, and S. Gauhar, Development of co-processed micro granules for direct compression. Int J Pharm Pharm Sci, 2011. 3(Suppl 2): p. 64-69.
28. Kushare, S.S. and S.G. Gattani, Microwave‐generated bionanocomposites for solubility and dissolution enhancement of poorly water‐soluble drug glipizide: in‐vitro and in‐vivo studies. Journal of pharmacy and pharmacology, 2013. 65(1): p. 79-93.
29. Hao, J., et al., Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. International journal of nanomedicine, 2011. 6: p. 683.
30. Nordström, J., I. Klevan, and G. Alderborn, A particle rearrangement index based on the Kawakita powder compression equation. Journal of pharmaceutical sciences, 2009. 98(3): p. 1053-1063.
31. Bi, Y., et al., Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull (Tokyo), 1996. 44(11): p. 2121-7.
32. McKenna, A. and D.F. McCafferty, Effect on particle size on the compaction mechanism and tensile strength of tablets. J Pharm Pharmacol, 1982. 34(6): p. 347-51.
33. 24-NF19, U., Friability. 2000, United State Pharmacopoeial Convention Inc., Rockville. p. 2148.
34. 24-NF19, U., Disintegration time. 2000, United State Pharmacopoeial Convention Inc., Rockville. p. 1941.
35. Patel, S.S., N.M. Patel, and M.M. Soniwala, Statistical development of a multifunctional directly compressible co-processed excipient using the melt agglomeration technique. Asian J Pharm Sci, 2009. 4: p. 340-356.
36. Kale, V., S. Gadekar, and A. Ittadwar, Particle size enlargement: Making and understanding of the behavior of powder (Particle) system. Systematic Reviews in Pharmacy, 2011. 2(2): p. 79.
37. Musa, H., A. Gambo, and P. Bhatia, Studies on some Physicochemical Properties of Native and Modified Starches from Digitaria iburua and Zea mays. Int J. Pharm Sci, 2011. 3(1): p. 28-31.
38. Alderborn, G. and C. Nyström, Studies on direct compression of tablets XIV. The effect of powder fineness on the relation between tablet permeametry surface area and compaction pressure. Powder technology, 1985. 44(1): p. 37-42.
39. Builders, P.F., et al., Novel multifunctional pharmaceutical excipients derived from microcrystalline cellulose–starch microparticulate composites prepared by compatibilized reactive polymer blending. International journal of pharmaceutics, 2010. 388(1): p. 159-167.
40. Rojas, J. and V. Kumar, Comparative evaluation of silicified microcrystalline cellulose II as a direct compression vehicle. International journal of pharmaceutics, 2011. 416(1): p. 120-128.
41. Bos, C., H. Vromans, and C. Lerk, Lubricant sensitivity in relation to bulk density for granulations based on starch or cellulose. International journal of pharmaceutics, 1991. 67(1): p. 39-49.
42. Heckel, R., Density-pressure relationships in powder compaction. Trans Metall Soc AIME, 1961. 221(4): p. 671-675.
43. Dolenc, A., et al., Advantages of celecoxib nanosuspension formulation and transformation into tablets. International journal of pharmaceutics, 2009. 376(1): p. 204-212.
44. Kawakita, K. and K.-H. Lüdde, Some considerations on powder compression equations. Powder technology, 1971. 4(2): p. 61-68.
45. Bolhuis, G. and K. Zuurman, Tableting properties of experimental and commercially available lactose granulations for direct compression. Drug development and industrial pharmacy, 1995. 21(18): p. 2057-2071.
46. Box, G.E. and D.W. Behnken, Some new three level designs for the study of quantitative variables. Technometrics, 1960. 2(4): p. 455-475.
47. Zidan, A.S., et al., Quality by design: Understanding the formulation variables of a cyclosporine A self-nanoemulsified drug delivery systems by Box–Behnken design and desirability function. International journal of pharmaceutics, 2007. 332(1-2): p. 55-63.
48. Edge, S., et al., The mechanical properties of compacts of microcrystalline cellulose and silicified microcrystalline cellulose. International journal of pharmaceutics, 2000. 200(1): p. 67-72.
49. Van Veen, B., et al., Compaction mechanism and tablet strength of unlubricated and lubricated (silicified) microcrystalline cellulose. European journal of Pharmaceutics and Biopharmaceutics, 2005. 59(1): p. 133-138.
50. Lerk, C., G. Bolhuis, and A. De Boer, Comparative evaluation of excipients for direct compression II. Pharm Weekbl, 1974. 109: p. 945-955.
51. Nyström, C., et al., Measurement of axial and radial tensile strength of tablets and their relation to capping. Acta Pharmaceutica Suecica, 1977. 15(3): p. 226-232.
52. Markl, D. and J.A. Zeitler, A review of disintegration mechanisms and measurement techniques. Pharmaceutical research, 2017. 34(5): p. 890-917.
53. Flores, L.E., R.L. Arellano, and J.J.D. Esquivel, Lubricant susceptibility of cellactose and Avicel PH-200: a quantitative relationship. Drug development and industrial pharmacy, 2000. 26(3): p. 297-305.
54. Rojas, J.J., J. Aristizabal, and M. Henao, Screening of several excipients for direct compression of tablets: a new perspective based on functional properties. Revista de Ciências Farmacêuticas Básica e Aplicada, 2013. 34(1): p. 17-23.
55. Pazesh, S., et al., Effect of milling on the plastic and the elastic stiffness of lactose particles. European Journal of Pharmaceutical Sciences, 2018. 114: p. 138-145.
56. Rumman, M., Understanding the functionality of MCC Rapid as an excipient for DC-Moving towards QbD. 2009.
57. Mustapha, M.A., C.I. Igwilo, and B.O. Silva, Influence of concentration of modified maize starch on compaction characteristics and mechanical properties of Paracetamol tablet formulation. Medical Journal of Islamic World Academy of Sciences, 2013. 21(3): p. 125-131.
Statistics
155 Views | 267 Downloads
How to Cite
Kushare, S., & Gattani, S. G. (2019). Design and Development of a Microwave Generated Lactose Monohydrate - Microcrystalline Cellulose Based Multifunctional Excipient Composites for Tablet Formulation using Box–Behnken Design. Journal of Drug Delivery and Therapeutics, 9(4), 1-17. https://doi.org/10.22270/jddt.v9i4.3123