Alur H H, Pather S I, Mitra A K, Johnston T P
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, Kansas City 64110, USA.
Pharm Dev Technol. 1999 Aug;4(3):347-58. doi: 10.1081/pdt-100101370.
The objective of this paper was to evaluate the mucoadhesive and sustained-release properties of the water-soluble gum obtained from Hakea gibbosa (hakea), for the formulation of buccal tablets. Flatfaced tablets containing hakea were formulated using chlorpheniramine maleate (CPM) as a model drug. Two types of tablets were prepared: uncoated tablets (type I) and tablets in which all but one face of the type I tablet was coated with hydrogenated castor oil (Cutina) using a compression coating technique (type II). In an attempt to explain the observed sustained-release effect, the potential for a chemical interaction between hakea and CPM was evaluated by FTIR, differential scanning calorimetry (DSC), UV spectroscopy, and acid-base titrations. Mathematical modeling of the CPM release data was developed to elucidate the mechanism of drug release. The mucoadhesive strength was evaluated by quantitating the force of detachment. Finally, the rates of water uptake and erosion were determined for the buccal tablets. The time required for 90% of the CPM to be released in vitro (t90%) was used as a basis for comparison. For formulations that did not contain hakea, the t90% was 14 min for both directly compressed and wet granulated tablets, whereas the t90% for wet granulated tablets containing 2 or 32 mg hakea/tablet was 36 and 165 min, respectively. Directly compressed tablets containing 2, 12, 22, and 32 mg hakea/tablet displayed t90% values of 48, 120, 330, and 405 min, respectively. DSC, FTIR, UV spectroscopy and acid-base titration experiments suggested the absence of chemical interactions. The force of detachment for directly compressed and wet granulated tablets increased from 0.70 +/- 0.3 to 4.08 +/- 0.52 N and from 0.65 +/- 0.28 to 3.94 +/- 0.31 N as the amount of hakea per tablet was increased from 0 to 32 mg, respectively, at a 5 N attachment compression force. The novel natural gum, hakea, may not only be utilized to sustain the release of CPM from a unidirectional-release buccal tablet, but it also exhibited excellent mucoadhesive properties. The mechanism by which CPM release was sustained was more likely due to slow relaxation of the hydrated hakea. The mucoadhesive strength can be modulated by altering the amount of hakea in the tablet.
本文的目的是评估从哈克木属植物（哈克木）中获得的水溶性胶的黏膜黏附性和缓释特性，用于口腔片剂的配方。以马来酸氯苯那敏（CPM）为模型药物，制备了含哈克木的平面片剂。制备了两种类型的片剂：未包衣片剂（I型）和采用压制包衣技术将I型片剂除一面外的所有面用氢化蓖麻油（Cutina）包衣的片剂（II型）。为了解释观察到的缓释效果，通过傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、紫外光谱和酸碱滴定法评估了哈克木与CPM之间发生化学相互作用的可能性。建立了CPM释放数据的数学模型以阐明药物释放机制。通过定量分离力来评估黏膜黏附强度。最后，测定了口腔片剂的吸水率和溶蚀率。以体外释放90%的CPM所需时间（t90%）作为比较依据。对于不含哈克木的制剂，直接压片和湿法制粒片剂的t90%均为14分钟，而每片含2或32毫克哈克木的湿法制粒片剂的t90%分别为36分钟和165分钟。每片含2、12、22和32毫克哈克木的直接压片的t90%值分别为48、120、330和405分钟。DSC、FTIR、紫外光谱和酸碱滴定实验表明不存在化学相互作用。在5 N的附着压缩力下，随着每片哈克木含量从0增加到32毫克，直接压片和湿法制粒片剂的分离力分别从0.70±0.3增加到4.08±0.52 N和从0.65±0.28增加到3.94±0.31 N。这种新型天然胶哈克木不仅可用于维持CPM从单向释放口腔片剂中的释放，还表现出优异的黏膜黏附性能。CPM释放得以维持的机制更可能是由于水合哈克木的缓慢松弛。黏膜黏附强度可通过改变片剂中哈克木的含量来调节。
