The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased C, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.
Acrylic Resins ; Adhesives ; Animals ; Chitosan ; Drug Carriers ; Drug Liberation ; In Vitro Techniques ; Intestinal Absorption ; Male ; Methylcellulose ; Panax notoginseng ; chemistry ; Plant Extracts ; administration & dosage ; metabolism ; pharmacokinetics ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; metabolism ; pharmacokinetics

OBJECTIVETo prepare matrine double-sensitive colon-specific pellets and study the factors affecting its quality and evaluateing the colon-specific effects of preparation.

METHODMatrine enzyme-sensitive pellets core were prepared by carboxymethyl konjac glucomannan as the main carrier material, and coated the core by acrylic resin II and III to prepare matrine double-sensitive colon-specific pellets. The prescription and technology of the matrine colon-specific pellets were studied by the single factor investigation, through the in vitro release test and coating rate determination.

RESULTThe optimized process conditions: FeCl3 concentration is 4.0 g x L(-1), chitosan concentration is 3.0 g x L(-1), carboxymethyl konjac glucomannan concentration is 20 g x L(-1), mixed gel solution pH value is 3. The release of matrine is less than 30% in the simulation of the upper gastrointestinal medium. The release of matrine is close to 100% in simulated full gastrointestinal medium, the coating weight is 7%.

CONCLUSIONThe prepared pellets have good colon positioning effect in vitro.

Acrylic Resins ; chemistry ; Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Chitosan ; chemistry ; Chlorides ; chemistry ; Colon ; metabolism ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Ferric Compounds ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Mannans ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Reproducibility of Results ; Tablets, Enteric-Coated ; Time Factors

In this paper, chloramphenicol was selected as a model drug to prepare in situ gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was evaluated using the surface dissolution imaging system. The results indicated that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel decreased significantly when the poloxamer concentration increased. The addition of the thickener reduced the intrinsic dissolution rate of chloramphenicol thermosensitive gel, wherein carbomer had the most impact. Different dilution ratios of simulated tear fluid greatly affected gel temperature, and had little influence on the intrinsic dissolution rate of chloramphenicol from the thermosensitive in situ gel. The pH of simulated tear fluid had little influence on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel. For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in weak acidic and neutral simulated tear fluids were slower than that in weak alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of chloramphenicol from in situ gel was dependent on formulation and physiological factors. With advantages of small volume sample required and rapid detection, the UV imaging method can be an efficient tool for the evaluation of drug release characteristics of ophthalmic in situ gel.
Acrylic Resins ; chemistry ; Anti-Bacterial Agents ; administration & dosage ; chemistry ; Chloramphenicol ; administration & dosage ; chemistry ; Drug Delivery Systems ; Gels ; chemistry ; Hydrogen-Ion Concentration ; Ophthalmic Solutions ; chemistry ; Poloxamer ; chemistry ; Solubility ; Spectrophotometry, Ultraviolet ; Temperature ; Viscosity

The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.
Acrylates ; administration & dosage ; chemistry ; pharmacokinetics ; Acrylic Resins ; administration & dosage ; chemistry ; pharmacokinetics ; Adhesiveness ; Administration, Buccal ; Animals ; Candidiasis, Oral ; drug therapy ; Cellulose ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Combinations ; Drug Stability ; Excipients ; Fluconazole ; administration & dosage ; chemistry ; pharmacokinetics ; Mouth Mucosa ; metabolism ; Polymers ; administration & dosage ; Sheep ; Tablets

The difference between absorption of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) after oral and oral cavity administration were studied respectively, and the compatible enhancer for oral cavity delivery system of both drugs was found. The LMWH and UFH films were prepared with two bioadhesive materials Carbopol and alginate sodium for oral cavity delivery. The activated partial thromboplastin time (APTT) was used to determine LMWH and UFH in plasma after oral, oral cavity and sc administration in rats. The results show that the enhancer (Labrasol) can increase the absorption of LMWH and UFH through oral cavity in rats but not obviously. The oral cavity iontophoretic delivery system is a useful method to improve the absorption of LMWH and UFH through oral cavity mucosa.
Absorption ; Acrylic Resins ; Administration, Oral ; Alginates ; chemistry ; Animals ; Anticoagulants ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Glucuronic Acid ; chemistry ; Glycerides ; Heparin ; administration & dosage ; pharmacokinetics ; Heparin, Low-Molecular-Weight ; administration & dosage ; pharmacokinetics ; Hexuronic Acids ; chemistry ; Injections, Intradermal ; Iontophoresis ; Male ; Mouth ; Organic Chemicals ; pharmacology ; Partial Thromboplastin Time ; Polyvinyls ; chemistry ; Rats ; Rats, Sprague-Dawley

To explore the influence of matrix materials in complicate ingredients on traditional Chinese medicine and investigate the excipients selection model based on balanced release characteristics of multicomponents, the influence of HPMC (K4M, K15M, K100M) and Carbomer (934P, 971P, 974P) was illustrated by testing in vitro release of ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in Panax notoginseng saponins (model drug, PNS). According to in vitro release results of PNS matrix tablets in water and artificial intestinal juice, the release curves were analyzed with Peppas equation and simulating factor (f). Significant differences in k value and n value among ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 existed in various formulations. The release behaviors from various excipients could be described with Non-Fickian transport or super Case II transport pattern. The f2 values for ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in 971P matrix tablet containing 30% Carbomer 971P were 74.91, 53.45, 57.89 in water and 79.35, 55.51, 51.89 in artificial intestinal juice, respectively. The release profiles fit for the regulation of FDA. The result revealed that the balanced release rates of Rg1, Rb1 and R1 in 971P matrix tablet were obtained.
Acrylates ; chemistry ; Acrylic Resins ; chemistry ; Delayed-Action Preparations ; Excipients ; chemistry ; Ginsenosides ; isolation & purification ; pharmacokinetics ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Saponins ; administration & dosage ; isolation & purification ; pharmacokinetics ; Tablets

This is a review of recent progress in the study on environment sensitive hydrogel based on cyclodextrin and their most recent and relevant applications in the intelligent drug delivery systems. Based on relevant literatures, the development of environment sensitive hydrogel responsive to physical, chemical and biochemical stimuli was introduced, involving their categorization, design principles, mechanism of action and potential application. Various new types of intelligent drug delivery system, which responds to various triggers, could be constructed by using the cyclodextrin-based environment sensitive hydrogel. They made it possible to control the drug release freely. Although these hydrogels are still at their research stage, they have attracted considerable interest in the intelligent drug delivery system.
Acrylic Resins ; Cyclodextrins ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Environment ; Hydrogels ; Hydrogen-Ion Concentration ; Light ; Polyethylene Glycols ; administration & dosage ; chemistry ; Polyvinyls ; administration & dosage ; chemistry ; Propylene Glycols ; administration & dosage ; chemistry ; Temperature

Ranolazine hydrochloride sustained-release tablet (RH-ST) was prepared and its release behavior in vitro was studied. The pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of RH-ST and ranolazine hydrochloride common tablets (RH-CT) as reference were compared. Three kinds of matrix, hydroxypropylmethylcellulose (HPMC K4M), ethylcellulose (EC 100cp) and acrylic resins (Eudragit RL100) were selected as functional excipients to keep ranolazine hydrochloride (RH) release for 12 hours. Through orthogonal designs, the polymers were quantified and the optimized cumulative release profile was obtained. The single oral dose of RH-ST 500 mg and RH-CT 333.3 mg was given to six dogs using a two way crossover design. Plasma levels were determined by LC-MS and the absorption fractions were calculated according to Loo-Riegelman formula. The steady-state concentration of RH in plasma of six dogs and its pharmacokinetics behaviors after continuous oral administration of RH-ST and RH-CT at different time intervals were studied by LC-MS. The steady-state pharmacokinetic parameters were computed by software program BAPP2.0. With the increase of the amount of the matrix, the drug release was decreased. The most important factor influencing drug release is the quantity of HPMC K4M. Drug release within the period (from 0 h to 12 h) fitted well into Higuchi model. The correlation coefficient (r) between the dissolution in vitro in release media of the distilled water and the absorptin fraction in vivo was 0.9550. To compare with RH-CT, RH-ST in vivo has a steady and slow release behavior, Tmax was obviously delayed (3.00 +/- 0.50) h and the relative bioavailability was over 80 percentage. The combined use of multiple polymers can decrease the tablet weight effectively, and the drug release rate can be decreased both in vitro and in vivo.
Acetanilides ; administration & dosage ; pharmacokinetics ; Acrylic Resins ; chemistry ; Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Cross-Over Studies ; Delayed-Action Preparations ; Dogs ; Excipients ; Female ; Hypromellose Derivatives ; Male ; Methylcellulose ; analogs & derivatives ; chemistry ; Piperazines ; administration & dosage ; pharmacokinetics ; Ranolazine ; Tablets

Albendazole is an orally administered broad-spectrum benzimidazole anthelmintic used against helminthiasis, hydatid cyst disease and neurocysticercosis. The objectives of this investigation are to develop a sustained release drug delivery system for albendazole, and to target its delivery to colon. Albendazole matrix tablets containing varying proportions of single and binary blends of four polymers; polyacrylic acid (carbopol 971), ethylcellulose (Etcell), eudragit L100-55 (EUD), and sodium carboxymethyl cellulose (CMC) were prepared by a modified wet granulation technique of kneading, extrusion and compaction. In vitro release profiles of albendazole was sequentially determined in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) without enzymes and in rat caecal content medium (RCCM) at 37 degrees C. The in vitro drug release from matrix tablets containing CMC and Etcell as single polymers showed initial burst effect in the first 2 h (>20% and 50% respectively), followed by a slow release in SIF. However, matrix tablets containing polymer blends showed that no appreciable drug release occurred up to 5 h. Drug release from tablets containing polymer blends in the dissolution medium containing rat caecal material suddenly increased to > or =30% after 5 h (RCCM), and reaching up to 90% in 24 h. Albendazole matrix tablets containing carbopol 971, Etcell, EUD, and CMC as single polymers and as blends were formulated for oral use. Drug release from the tablet matrices containing carbopol alone, binary blends of carbopol/Etcell, and CMC/EUD were found to be very slow and dependent on polymer concentration. Matrix tablets containing blends of these polymers formulated using kneading, extrusion and compaction technique could provide sustained drug release and can be utilized in the colonic delivery of albendazole.
Acrylic Resins ; chemistry ; Administration, Oral ; Albendazole ; administration & dosage ; pharmacokinetics ; Animals ; Anthelmintics ; administration & dosage ; pharmacokinetics ; Carboxymethylcellulose Sodium ; chemistry ; Cellulose ; analogs & derivatives ; chemistry ; Colon ; metabolism ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Drug Compounding ; Drug Delivery Systems ; In Vitro Techniques ; Male ; Rats ; Tablets ; Technology, Pharmaceutical ; methods

To study the role of meridians in the formation and development of diseases, a pathological model of obstructed channel was established by injecting polyacrylamide hydrogel. The effects of blocking low hydraulic resistance channel (LHRC), produced by injecting polyacrylamide hydrogel and by injecting normal saline, were compared by examining the change in transmission of interstitial fluid pressure wave. The results showed that there was significant decrease (P < 0.01) in interstitial fluid pressure wave after more than 0.5 ml polyacrylamide hydrogel was injected into the channel, whereas no significant changes were found after normal saline was injected or when the hydrogel was outside the channel. The above findings demonstrate that the low hydraulic resistance channel can be blocked by injecting certain amount of polyacrylamide hydrogel and a pathological model of obstructed channel has been established preliminarily.
Acrylic Resins ; administration & dosage ; pharmacology ; Animals ; Male ; Medicine, Chinese Traditional ; methods ; Meridians ; Random Allocation ; Swine ; Swine, Miniature