Polymers in Medicine
2018, vol. 48, nr 2, July-December, p. 83–90
doi: 10.17219/pim/104462
Publication type: original article
Language: English
Download citation:
Study of the influence of cellulose derivatives on physical and analytical attributes of a drug product belonging to BCS class II
1 Gedeon Richter Sp. z o.o., Research and Development Department, Grodzisk Mazowiecki, Poland
Abstract
Background. Cellulose microcrystalline (MCC), hydroxypropyl methylcellulose (HPMC) and croscarmellose sodium are cellulose derivatives which are widely used in pharmaceutical technology. Although they are inert pharmaceutical ingredients, they can influence the release profile of an active substance from the dosage form depending on their distribution, type and quantity used in the formulation.
Objectives. The aim of the present investigation was to examine the effect of chosen cellulose derivatives on the physical and analytical attributes of a drug product containing an active substance of Biopharmaceutics Classification System (BCS) class II.
Material and Methods. The tablets were prepared using the wet granulation technology. The batches differed in the amount and grade of HPMC, the type of MCC and the distribution of croscarmellose sodium. The granule properties as well as physical (tablet hardness, disintegration time, friability) and analytical (dissolution profile in different media) attributes of the tablets were examined.
Results. The flow characteristics were satisfying in the case of all prepared batches. However, the differences in flow properties were visible, especially in the cases where MCC of coarser particles was replaced with MCC of finer particles. The type of MCC used in the product formula also had a significant influence on the drug product dissolution profile. The batches in which MCC of finer particles was used had substantially better results, regardless of HPMC viscosity type and the distribution of croscarmellose sodium between the inner and outer phase. What is more, the differences in the results between batches of different MCC types were especially visible in dissolution conditions, i.e., 0.1N hydrochloric acid (HCl).
Conclusion. By choosing the right type, quantity and distribution of cellulose derivatives, it was possible to obtain the optimal formula of the drug product similar to in-vitro conditions to the reference drug. Out of all the tested excipients, the type of cellulose microcrystalline was found to have the most critical influence on both physical and analytical properties of the pharmaceutical formulation.
Key words
wet granulation, dissolution profile, cellulose derivatives, drug formulation technology
References (11)
- Halib N, Perrone F, Cemazar M, et al. Potential applications of nanocellulose-containing materials in the biomedical field. Materials. 2017;10:977.
- Shokri J, Adibkia K. Application of Cellulose and Cellulose Derivatives in Pharmaceutical Industries. In: Van De Ven TGM, ed. Cellulose Medical, Pharmaceutical and Electronic Applications. Intech; 2013.
- Kubiak-Tomaszewska G, Tomaszewski P, Pachecka J. Hypromellose in pharmaceutical technology of capsules and other medicinal product dosage forms. Pediatr Med Rodz. 2011;7(3):271–276.
- Rawat S, Derle DV, Fukte SR, Shinde PR, Parve BS. Superdisintegrants: An overview, World J Pharm Pharm Sci. 2014;3(5):263–278.
- Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. London; 2009:129–133, 206–208.
- Hamed E, Moe D, Khankari R, Hontz J. Binders and Solvents. In: Parikh DM, Raton B, ed. Handbook of Pharmaceutical Granulation Technology. 2nd ed. North Carolina, Pinehurs: PharmaceuTech Inc.; 2005:109–125.
- US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Waiver of in Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for industry. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research; 2017.
- Khadka P, Kim JRH, Kim I, et al. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. AJPS. 2014;9(6)304–316.
- US Department of Health and Human Services Food and Drug Administration Centre for Drug Evaluation and Research. Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms. US Department of Health and Human Services Food and Drug Administration Centre for Drug Evaluation and Research; 1997.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Biopharmaceutics Classification System-Based Biowaivers M9 [draft version]. Geneva: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 2018.
- European Pharmacopeia. 7th Edition. Vol. 1. https://pl.scribd.com/document/367962556/European-Pharmacopoeia-7-0-Vol-1-pdf