Domosławska Magdalena, Pawlak-Morka Renata, Dobrzyński Łukasz, Herda Monika
Gedeon Richter Sp. z o.o., Research and Development Department, Grodzisk Mazowiecki, Poland.
Polim Med. 2018 Jul-Dec;48(2):83-90. doi: 10.17219/pim/104462.
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.
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.
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.
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).
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.
微晶纤维素（MCC）、羟丙基甲基纤维素（HPMC）和交联羧甲基纤维素钠是纤维素衍生物，在制药技术中广泛应用。尽管它们是惰性药用成分，但根据其在制剂中的分布、类型和用量，会影响活性物质从剂型中的释放情况。
本研究旨在考察所选纤维素衍生物对含有生物药剂学分类系统（BCS）II类活性物质的药品的物理和分析属性的影响。
采用湿法制粒技术制备片剂。各批次在HPMC的用量和等级、MCC的类型以及交联羧甲基纤维素钠的分布方面存在差异。考察了颗粒性质以及片剂的物理属性（片剂硬度、崩解时间、脆碎度）和分析属性（在不同介质中的溶出曲线）。
所有制备批次的流动性均令人满意。然而，流动性存在明显差异，尤其是在粗颗粒MCC被细颗粒MCC替代的情况下。产品配方中使用的MCC类型对药品溶出曲线也有显著影响。无论HPMC粘度类型以及交联羧甲基纤维素钠在内相和外相之间的分布如何，使用细颗粒MCC的批次结果都明显更好。此外，不同MCC类型批次之间的结果差异在溶出条件下，即0.1N盐酸（HCl）中尤为明显。
通过选择合适的纤维素衍生物类型、用量和分布，可以获得与参比药品体外条件相似的药品最佳配方。在所有测试辅料中，微晶纤维素类型对药物制剂的物理和分析性质影响最为关键。
