Amorphous solid dispersions(ASDs)are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs.Various approaches have been employed to produce ASDs and novel techniques are emerging.This ...Amorphous solid dispersions(ASDs)are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs.Various approaches have been employed to produce ASDs and novel techniques are emerging.This review provides an updated overview of manufacturing techniques for preparing ASDs.As physical stability is a critical quality attribute for ASD,the impact of formulation,equipment,and process variables,together with the downstream processing on physical stability of ASDs have been discussed.Selection strategies are proposed to identify suitable manufacturing methods,which may aid in the development of ASDs with satisfactory physical stability.展开更多
The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. ...The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.展开更多
This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating p...This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxime Axetil (CFA) particles, 200–400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), and 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation and drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing and the ease of scaling-up.展开更多
过饱和给药系统(supersaturated drug delivery system,SDDS)是利用药物的高能态形式或快速溶出在胃肠道中形成过饱和溶液并维持足够长时间以促进难溶性药物口服吸收的一类给药系统。过饱和溶液属于热力学不稳定体系,易出现药物结晶析...过饱和给药系统(supersaturated drug delivery system,SDDS)是利用药物的高能态形式或快速溶出在胃肠道中形成过饱和溶液并维持足够长时间以促进难溶性药物口服吸收的一类给药系统。过饱和溶液属于热力学不稳定体系,易出现药物结晶析出而达不到促吸收的目的。因此,有效维持过饱和溶液稳定是SDDS研发的重点之一。聚合物型过饱和给药系统是以聚合物为沉淀抑制剂的SDDS,聚合物的存在能有效抑制药物结晶沉淀的发生,对于维持过饱和溶液的稳定具有显著作用。然而不同的聚合物有着不同的沉淀抑制能力,目前对于聚合物维持药物溶液过饱和态的机制尚不清楚。因此,本文对聚合物型过饱和给药系统的促吸收机制、体外评价及其研究现状进行综述,以期为SDDS的理性化设计提供参考。展开更多
基金supported,in whole or in part,by the Bill&Melinda Gates Foundation[No.OPP1159809,USA]supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award(No.R01AI132681,USA)
文摘Amorphous solid dispersions(ASDs)are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs.Various approaches have been employed to produce ASDs and novel techniques are emerging.This review provides an updated overview of manufacturing techniques for preparing ASDs.As physical stability is a critical quality attribute for ASD,the impact of formulation,equipment,and process variables,together with the downstream processing on physical stability of ASDs have been discussed.Selection strategies are proposed to identify suitable manufacturing methods,which may aid in the development of ASDs with satisfactory physical stability.
基金the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(no.2015R1A5A1008958)supported by the Industry Technology Development Program(10077593)funded by the Ministry of Trade,Industry&Energy(MOTIE,Korea)。
文摘The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.
基金"863 Plan" of China(grant no. 2001AA218061, no. 2004AA218042,and no.2006AA030202)the National Natural Science Foundation(NSF) of China (grant no. 20146002,no.20236020,and no.20325621)Nano Materials Technology Pte. Ltd., Singapore
文摘This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxime Axetil (CFA) particles, 200–400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), and 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation and drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing and the ease of scaling-up.
文摘过饱和给药系统(supersaturated drug delivery system,SDDS)是利用药物的高能态形式或快速溶出在胃肠道中形成过饱和溶液并维持足够长时间以促进难溶性药物口服吸收的一类给药系统。过饱和溶液属于热力学不稳定体系,易出现药物结晶析出而达不到促吸收的目的。因此,有效维持过饱和溶液稳定是SDDS研发的重点之一。聚合物型过饱和给药系统是以聚合物为沉淀抑制剂的SDDS,聚合物的存在能有效抑制药物结晶沉淀的发生,对于维持过饱和溶液的稳定具有显著作用。然而不同的聚合物有着不同的沉淀抑制能力,目前对于聚合物维持药物溶液过饱和态的机制尚不清楚。因此,本文对聚合物型过饱和给药系统的促吸收机制、体外评价及其研究现状进行综述,以期为SDDS的理性化设计提供参考。
