Akbari Jafar, Nokhodchi Ali, Farid Djavad, Adrangui Massoud, Siahi-Shadbad Mohammad Reza, Saeedi Majid
Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran(Sari) Medical Sciences University, Sari, Iran.
Farmaco. 2004 Feb;59(2):155-61. doi: 10.1016/j.farmac.2003.11.011.
The buccal mucosa has been investigated for local and systemic delivery of therapeutic peptides and other drugs that are subjected to first-pass metabolism or are unstable within the rest of the gastrointestinal tract. Propranolol hydrochloride (propranolol HCl) is subjected to first-pass effect, therefore formulation of buccal-adhesive dosage form can circumvent this effect. The effect of lactose (a soluble excipient) and dicalcium phosphate (DCP) (an insoluble excipient) on dissolution rate, kinetic of release and adhesion force of buccal-adhesive tablets of propranolol HCl were evaluated. Each tablet composed of 80 mg propranolol HCl, 80 mg hydroxypropylmethylcellulose (HPMC) K4M, polycarbophil AA1 and lactose or DCP with different ratios. The results showed that the presence of the fillers increased dissolution rate of the drug. The release data also showed that the effect of lactose on the dissolution rate was greater than the DCP. Kinetic release of propranolol HCl from buccal-adhesive matrices was affected by the different ratios of polymers and fillers. The fillers reduced the bioadhesion force and this effect was more considerable in formulation containing DCP. In order to determine the mode of release, the data were analyzed based on the equation Q =kt(n). The results showed that an increase in the concentration of HPMC K4M resulted in a reduction in the value of n. The value of n was not significantly affected by an increase in the concentration of lactose or DCP. The values of n in this study were calculated to be between 0.461 and 0.619, indicating both diffusional release and erosional mechanism.
颊黏膜已被用于研究治疗性肽和其他药物的局部和全身给药，这些药物会经历首过代谢或在胃肠道其他部位不稳定。盐酸普萘洛尔会经历首过效应，因此颊黏膜黏附剂型的制剂可以规避这种效应。评估了乳糖（一种可溶性辅料）和磷酸氢钙（DCP）（一种不溶性辅料）对盐酸普萘洛尔颊黏膜黏附片的溶出速率、释放动力学和黏附力的影响。每片由80mg盐酸普萘洛尔、80mg羟丙基甲基纤维素（HPMC）K4M、聚卡波非AA1和不同比例的乳糖或DCP组成。结果表明，填充剂的存在提高了药物的溶出速率。释放数据还表明，乳糖对溶出速率的影响大于DCP。盐酸普萘洛尔从颊黏膜黏附基质中的释放动力学受聚合物和填充剂不同比例的影响。填充剂降低了生物黏附力，这种效应在含有DCP的制剂中更为显著。为了确定释放模式，根据方程Q = kt(n)对数据进行分析。结果表明，HPMC K4M浓度的增加导致n值降低。n值不受乳糖或DCP浓度增加的显著影响。本研究中n值计算在0.461至0.619之间，表明既有扩散释放又有溶蚀机制。
