Suram Dinesh, Veerabrahma Kishan
Nanotechnology and Novel Drug Delivery Laboratory, Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India.
AAPS PharmSciTech. 2022 Apr 22;23(5):123. doi: 10.1208/s12249-022-02272-2.
Lovastatin (Lov) is a lipid-lowering agent, with 5% bioavailability (BA) due to extensive first pass metabolism and poor solubility. To enhance dissolution and in vivo effects, Lov solid self microemulsifying drug delivery system (SMEDDS) and liquisolid systems were developed and evaluated to select superior one. Solubilities were determined in oils, surfactants, and cosurfactants. Ternary phase diagrams were constructed and selected the one which showed maximum emulsion zone. In vitro dissolution, DSC, SEM and PXRD studies were used to characterize the developed formulations. In vivo studies were conducted on optimal formulations in wistar rats. Based on solubilities, Capmul PG8 and Capmul MCM were preferred as oils, Labrasol and Transcutol P as surfactant and cosurfactant. Here, Syloid XDP carrier showed better adsorption capacity among others, hence was used in optimal solid SMEDDS (SX) and liquisolid (LS) formulations. Dissolution study results showed significant improvement in release when compared to pure drug. DSC, SEM, and PXRD results indicated the loss of drug crystallinity in optimal formulations. In pharmacokinetic (PK) study, SX and LS showed 2.57 and 1.43 fold improvements in AUC, when compared to that of coarse suspension (CS). In pharmacodynamic (PD) study, hyperlipidemia was induced by Triton X-100. CS and LS treatments showed a decline in hyperlipidemic levels at 4 h. But, SX-treated group showed early onset of decline at 2 h. Further, the duration of anti-hyperlipidemia was at least 12 h extra when compared to CS and LS. This study confirmed the superiority of SX over LS in PK and PD effects.
洛伐他汀（Lov）是一种降脂药物，由于广泛的首过代谢和低溶解度，其生物利用度（BA）为5%。为了提高溶解度和体内效果，开发并评估了洛伐他汀固体自微乳化药物递送系统（SMEDDS）和液固系统，以选择更优的系统。测定了其在油、表面活性剂和助表面活性剂中的溶解度。构建了三元相图，并选择了显示最大乳液区的相图。采用体外溶出度、差示扫描量热法（DSC）、扫描电子显微镜（SEM）和粉末X射线衍射（PXRD）研究对所开发的制剂进行表征。在Wistar大鼠上对最佳制剂进行了体内研究。基于溶解度，优选Capmul PG8和Capmul MCM作为油相，Labrasol和Transcutol P作为表面活性剂和助表面活性剂。在此，Syloid XDP载体在其他载体中表现出更好的吸附能力，因此被用于最佳固体SMEDDS（SX）和液固（LS）制剂中。溶出度研究结果表明，与纯药物相比，药物释放有显著改善。DSC、SEM和PXRD结果表明，最佳制剂中药物结晶度降低。在药代动力学（PK）研究中，与粗悬浮液（CS）相比，SX和LS的曲线下面积（AUC）分别提高了2.57倍和1.43倍。在药效学（PD）研究中，用Triton X-100诱导高脂血症。CS和LS处理组在4小时时高脂血症水平下降。但是，SX处理组在2小时时就出现了早期下降。此外，与CS和LS相比，抗高脂血症的持续时间至少延长了12小时。本研究证实了SX在PK和PD效应方面优于LS。
