Poka Madan Sai, Milne Marnus, Wessels Anita, Aucamp Marique
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa.
Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
Pharmaceutics. 2025 Mar 2;17(3):321. doi: 10.3390/pharmaceutics17030321.
Carbamazepine (CBZ) is a Biopharmaceutical Classification System (BCS) class II drug, that is practically insoluble in water, influencing the oral bioavailability. Polyols are highly hydrophilic crystalline carriers studied for their success in developing solid dispersions (SDs) for improved solubility and dissolution rate. Polyols are generally regarded as safe (GRAS) and maltitol (MAL), xylitol (XYL) and sorbitol (SOR) are among the approved polyols for market use. While xylitol (XYL) and sorbitol, have shown promise in improving the solubility and dissolution rates of poorly soluble drugs, their full potential in the context of improving the solubility of carbamazepine have not been thoroughly investigated. To the best of our knowledge, maltitol (MAL) was not studied previously as a carrier for preparing SDs. Hence, the purpose of this study was to investigate their use in the preparation of CBZ SDs by the fusion method. CBZ-polyol SDs were prepared in varying molar ratios (2:1, 1:1 and 1:2) and characterised for solid-state nature, solubility and in-vitro dissolution rate. Solid-state characterisation of the CBZ-polyol SDs revealed the existence of the SDs as continuous glass suspensions with fine CBZ crystallites suspended in the amorphous polyol carriers. Among the polyols studied, XYL exhibited good miscibility with CBZ and showed significant improvement in the solubility and dissolution rate. The prepared SDs showed a 2 to 6-folds increase in CBZ solubility and 1.4 to 1.9-folds increase in dissolution rate in comparison with pure CBZ. The study explains the possible use of polyols (XYL and SOR) based SDs of BCS Class II drugs with good glass forming ability for enhanced solubility and dissolution.
卡马西平（CBZ）是生物药剂学分类系统（BCS）中的II类药物，在水中几乎不溶，这影响了其口服生物利用度。多元醇是高度亲水性的结晶载体，因其在开发用于提高溶解度和溶出速率的固体分散体（SDs）方面取得的成功而受到研究。多元醇通常被认为是安全的（GRAS），麦芽糖醇（MAL）、木糖醇（XYL）和山梨醇（SOR）是已获批准可用于市场的多元醇。虽然木糖醇（XYL）和山梨醇在提高难溶性药物的溶解度和溶出速率方面已显示出前景，但它们在改善卡马西平溶解度方面的全部潜力尚未得到充分研究。据我们所知，麦芽糖醇（MAL）此前未被作为制备固体分散体的载体进行研究。因此，本研究的目的是通过熔融法研究它们在制备CBZ固体分散体中的应用。以不同摩尔比（2:1、1:1和1:2）制备了CBZ - 多元醇固体分散体，并对其固态性质、溶解度和体外溶出速率进行了表征。CBZ - 多元醇固体分散体的固态表征显示，固体分散体以连续玻璃悬浮液的形式存在，细小的CBZ微晶悬浮在无定形多元醇载体中。在所研究的多元醇中，XYL与CBZ表现出良好的混溶性，并在溶解度和溶出速率方面有显著提高。与纯CBZ相比，制备的固体分散体使CBZ的溶解度提高了2至6倍，溶出速率提高了1.4至1.9倍。该研究解释了具有良好玻璃形成能力的基于多元醇（XYL和SOR）的BCS II类药物固体分散体在提高溶解度和溶出方面的可能应用。
