To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

We prepared the isosorbide-5-mononitrate pulsatile controlled-release pellets (PCRP) and studied the influencing factors in vitro. The isosorbide-5-mononitrate (5-ISMN) pellets prepared by extrusion-spheronization technology were coated with swelling material as the inner coating swelling layer, and with ethylcellulose aqueous dispersion as the outer coating controlled layer. The influences of the coating materials of the swelling layer, the coating levels of the swelling layer and controlled layer,and the pH values of the media on the release of 5-ISMN from PCRP were investigated. The drug release from the pellets was pulsatile. The ISMN-5-PCRP, with a lag time of 5 h and more than 80% released within the following 1.5 h,were prepared by using the low-substituted hydroxypropyl cellulose as the inner swelling layer with 15% (weight) in coating thickness, and the ethylcellulose aqueous dispersion as the outer controlling layer with 13% (weight) in coating thickness.
Capsules ; Cellulose ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Hypromellose Derivatives ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry

OBJECTIVETo investigate the release model of insoluble drug carbamazepine (CBM) based on HPMC matrix tablets.

METHODSCBM release profile from matrices and HPMC erosion rate were determined.

RESULTThe mathematical model by matrix erosion rate and drug release from HPMC K15M were established for the fractional HPMC and CBM released as M(P(t))/M(P(infinity))=-[0.8095ln((t))+1.2775]Meq((-0.0622t-0.305)) and M(d(t))/M(d(infinity))=-[0.1891t-0.1294]Meq(-0.9326). In comparison with the data of HPMC K4M matrix erosion and CBM release from HPMC K4M matrices, theoretical value agreed well with experimental data.

CONCLUSIONThe two mathematical models can be satisfactorily applied to insoluble drug release, which is governed by matrix erosion.

Carbamazepine ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Hypromellose Derivatives ; Methylcellulose ; administration & dosage ; analogs & derivatives ; Models, Theoretical ; Solubility ; Tablets

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.
Administration, Oral ; Biological Availability ; Caco-2 Cells ; Drug Delivery Systems ; Emulsions ; Humans ; Methylcellulose/analogs & derivatives* ; Nanoparticles ; Particle Size ; Silybin ; Solubility

AIMTo elucidate the mechanism and to present suitable models for the release of sodium ferulate (SF) from hydroxypropyl methylcellulose (HPMC) based matrix tablets.

METHODSThe characteristics and mechanisms of drug release were analyzed from the point of thermodynamic, swelling and diffusion effect. Despite the classical equation of Higuchi, the semi-empirical power law and quadratic curve were also adopted to analogize the release of SF from HPMC based tablets in vitro.

RESULTSThe first release stage of SF was mainly controlled by Fick diffusion, and the rest SF released mainly according to case II transport process caused by the swelling effect of HPMC. The decreased Tg of HPMC, resulted from the entered water, enhanced the release of SF. The power law was possible for the first released 60% SF, but unfit for the last 40% SF. The quadratic curve expressed equation can illuminate the release of SF.

CONCLUSIONFor the HPMC system, drug release undertakes the Fick diffusion process followed by the extend of polymer chain. The nonlinear quadratic equation might be valuable to explain the entire drug release from HPMC-based delivery system.

Chemistry, Pharmaceutical ; Coumaric Acids ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Diffusion ; Drug Carriers ; Drug Delivery Systems ; Kinetics ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Oxazines ; Solubility ; Tablets

AIMTo develop a novel pulsatile drug delivery system of which the lag-time is controlled by an erodible plug (EP) and evaluate its release characteristics in vitro.

METHODSThe impermeable capsule body was prepared by fulfilling method and the drug tablet and the erodible plug were made by wet granulating compression. Tetramethylpyrazine phosphate (TMPP) pulsincap capsule was prepared by sealing the drug tablet and fillers inside the impermeable capsule body with the EP. The influence factors on the lag-time such as the EP pharmaceutical properties and the dissolution condition were investigated by dissolution testing.

RESULTSBoth the composition and the weight of EP influenced the lag-time of the tetramethylpyrazine phosphate pulsincap capsule significantly. The lag-time prior to the drug release was enhanced when the content of gel-forming excipient (hydroxypropylmethylcellulose, HPMC) in the EP or the weight of EP was increased. The hardness of EP showed minor influence on the lag-time. In addition, the lag-time was shortened when the paddle speed was higher, while the pH value of the dissolution medium exhibited no significant influence on it.

CONCLUSIONTo meet the chronotherapeutic requirements, a pulsatile drug delivery system with a suitable lag-time can be achieved by adjusting the composition and the EP weight.

Calcium Channel Blockers ; administration & dosage ; Capsules ; Delayed-Action Preparations ; Drug Delivery Systems ; Lactose ; analogs & derivatives ; Methylcellulose ; analogs & derivatives ; Oxazines ; Pyrazines ; administration & dosage ; Technology, Pharmaceutical

AIMTo prepare dilitazem hydrochloride delayed-onset, sustained release tablet, which can not only provide the delay in release start, but also the constant release rate after a lag time. To analyze release mechanism and investigate the effect of outershell compositions on release behavior.

METHODSThe delayed-onset, sustained release tablets were prepared by dry-compression coated technology. The release profiles of uncoated cores and presscoated tablets were compared. Two parameters, time-lag (Tlag) and release rate (k), were used to evaluate the influence of factors, such as the amount of hydroxypropylmethylcellulose (HPMC) and poly-vinyl-pyrrolidinone (PVP) K30, the viscosity of ethylcellulose (EC) and HPMC, and the compression load on diltazam hydrochloride (DIL) release. Higuchi equation and Peppa's equation were used to analyze release mechanism.

RESULTSWith the increase of HPMC amount or HPMC viscosity, Tlag was prolonged and k was decreased; With the increase of PVP K30 amount, Tlag was shortened and k was increased; EC viscosity and compression load above certain degree showed no effect on DIL release.

CONCLUSIONThe drug release from delayed-release tablet is controlled by erosion mechanism, Tlag is determined by the erosion rate of outer-shell.

Cellulose ; chemistry ; Delayed-Action Preparations ; Diltiazem ; administration & dosage ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Oxazines ; Polyvinyls ; chemistry ; Pyrrolidinones ; chemistry ; Tablets ; administration & dosage ; chemistry ; Technology, Pharmaceutical ; Viscosity

For the purpose of preparing the ondansetron hydrochloride sustained-release tablets and studying the influencing factors, we prepared the ondansetron hydrochloride sustained-release tablets, using hydroxypropylmethylcellose (HPMC) as the matrix material. Then we investigated the effects of the viscosity and amount of HPMC,the sort of fillers, the preparation methods, the alcohol content in adhesives, and the pH of the dissolving solution on the release of ondansetron hydrochloride from sustained-release tablets. On the basis of pharmaceutical preformulation studies,the best formulation and preparation methods were screened out according to orthogonal experiment design method. The release behavior of the tablets followed the Higuchi equation. The viscosity of HPMC,the sort of fillers and the rotation speed had no significant effects on the release of ondansetron hydrochloride sustained-release tablets,while the preparation methods, the alcohol content in adhesives and the pH of the dissolving solution influcenced the release of ondansetron hydrochloride sustained-release tablets significantly. Ondansetron hydrochloride sustained-release tablets had good drug relase behavior for in 12 h in vitro.
Delayed-Action Preparations ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Models, Chemical ; Ondansetron ; administration & dosage ; chemistry ; Pharmaceutical Preparations ; chemistry ; Tablets ; Viscosity

The hydroxypropyl methylcellulose (HPMC) matrix tablet containing metoprolol succinate (MS) as a model drug was obtained by wet method compression tablet. The effects of the amount and viscosity of HPMC, the preparation method, compressing pressure, the amount of ethycellulose (EC), the pH of dissolution medium and the speed of basket rotation on the drug release from the matrix tablets were evaluated. The results showed that the release rate of metoprolol succinate from HPMC matrix tablets followed Higuchi equation. The release mechanism was in line with the synthetical effect of diffusion and corrosion. Drug release was influenced by the amount and viscosity of HPMC, the amount of EC in matrices, the preparation method and compressing pressure, etc. Drug release was not influenced by the pH of dissolution medium used, and not by the speed of basket rotation, either.
Delayed-Action Preparations ; Drug Compounding ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; chemistry ; Metoprolol ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Pharmaceutic Aids ; chemistry ; Pharmaceutical Preparations ; chemistry ; Tablets ; Viscosity

OBJECTIVETo study the influence of the sustained release excipient on the release rate of ginsenoside Rg1 and ginsenoside Rb1 in sustained-release tablet of Panax Notoginsenosides.

METHODThe release rate of ginsenoside Rg1 and ginsenoside Rb1 in different matrix tablets with different excipient (HPMC, EC), different viscosity of EC (RT-50, RT-100), different ratio of EC in matrix tablet were detected.

RESULTAll above different factors influence the release rate of ginsenoside Rg1 and ginsenoside Rb1 and brought them different release curve.

CONCLUSIONEmphasis should be laid on the different release characteristic of different active compounds in active fraction.

Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Drugs, Chinese Herbal ; administration & dosage ; Excipients ; chemistry ; Ginsenosides ; chemistry ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Oxazines ; Panax ; Plants, Medicinal ; Tablets