Evaluation of Monolithic Osmotic Tablet System for Nifedipine Delivery In Vitro and In Vivo

Abstract

The aim of this study was to evaluate the monolithic osmotic tablet system (MOTS) containing a solid dispersion with the practically water-insoluble drug nifedipine in vitro and in vivo. In the drug release study in vitro, the release profiles of this system had almost zero-order kinetics. The influences of tablet formulation variables, sizes of the delivery orifice, membrane variables, and values of pH in the dissolution medium on nifedipine release from MOTS have been investigated. The results provided evidence that the tablet core played an important role in MOTS. While orifice sizes and membrane variables affected the nifedipine release rate, MOTS was independent of the dissolution medium. The appropriate orifice size was found to be in the range of 0.5–1.0 mm. The coating membrane incorporating hydrophilic polyethylene glycol (PEG) formed a porous structure. The human pharmacokinetics and relative bioavailability of MOTS containing nifedipine were compared with a commercial Adalat® osmotic tablet system containing an equivalent dose of nifedipine following an oral single dose of 30 mg given to each of 11 healthy volunteers in an open, randomized crossover study in vivo. The relative bioavailability for MOTS was 112%. There was no statistically significant difference in the pharmacokinetic parameters between two dosage forms. It is concluded that the monolithic osmotic tablet controlled release system is feasible for a long-acting preparation as a once-daily treatment.     

In Vitro and In Vivo Evaluation of Glibenclamide in Solid Dispersion Systems

The purpose of this work is to improve the dissolution and bioavailability characteristics of glibenclamide as compared to Daonil® tablets (Hoechst). Solid dispersions of glibenclamide in Gelucire 44/14 (Formula 1) and in polyethylene glycol 6000 (PEG 6000) (Formula 2) were prepared by fusion method. In vitro dissolution studies showed that the dispersing systems containing glibenclamide and Gelucire 44/14 or PEG 6000 gave faster dissolution rates than the reference product Daonil. The in vivo bioavailability study was assessed in six healthy male volunteers in crossover design with a 1‐week washout period. Both formulas were found to be significantly different from Daonil with regard to the extent of absorption as indicated by the area under serum concentration‐time curve. Both formulas are not significantly different from Daonil with respect to time of peak plasma concentration (T_max). It is concluded from this pilot study that the ranking of the in vitro dissolution is similar to the ranking of in vivo availability. The ranking of the three preparations in term of dissolution rate and extent of absorption is as follows: Formula 2?>?Formula 1?>?Daonil.     

卤虫体外转录模型及其转录活性检测

通过改进的细胞核提取方法,获取了纯度较高的细胞核并建立了卤虫体外转录系统模型。将待基因与含转录起始位点的报告基因的编码序列相连,制备成体外转录模块。由于体外转录所产生的RNA量极少,需要一种灵敏的方法检测生成的RNA。应用了RT－PCR技术鉴定体外转录产物的方法能有效解决这一问题。转录后,用无RNase的DNaseI将DNA模板完全降解;生成的RNA经逆转录反应合成cDNA,再以cDNA为模板,用相应的引物进行PCR扩增,琼脂糖凝胶电泳检测结果。该法灵敏度高,操作简单安全,无需同位素。     

Development of Sustained-Release Tablets Containing Sodium Valproate: In Vitro and In Vivo Correlation

ABSTRACT

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C_max was only 20% higher than the fasting C_max. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.     

In Vivo and In Vitro Degradation Behavior of Magnesium Alloys as Biomaterials

The corrosion behavior of pure Mg,AZ31,and AZ91D were evaluated in various in vitro and in vivo environments to investigate the potential application of these metals as biodegradable implant materials.DC polarization tests and immersion tests were performed in different simulated body solutions,such as distilled(DI) water,simulated body fluid(SBF) and phosphate buffered solution(PBS).Mg/Mg alloys were also implanted in different places in a mouse for in vivo weight loss and biocompatibility investigations.The in vivo subcutis bio-corrosion rate was lower than the corrosion rate for all of the in vitro simulated corrosive environments.The Mg/Mg alloys were biocompatible based on histology results for the liver,heart,kidney,skin and lung of the mouse during the two months implantation.Optical microscopy and scanning electron microscopy were carried out to investigate the morphology and topography of Mg/Mg alloys after immersion testing and implantation to understand the corrosion mechanisms.     

Production of an Extremly Low Dose Procaterol HCl Preparation by Fluidized-Bed Coating Method: In Vitro and In Vivo Evaluation

Abstract

A convenient and reliable method to prepare procaterol HCl oral dosage form at an extremely low dosage (25 µg/cap) is presented in this paper. Procaterol HCl was mixed with the film-forming agent hydroxypropyl methylcellulose in an aqueous solution, which was then spray-coated on sugar spheres (Nu-pareil PG 20/25) to produce procaterol HCl pellets. The IR spectra of coated and noncoated pellets indicated that procaterol HCl was coated on the sugar spheres successfully with a weight increment less than 1%. Most of the coated pellets were able to pass through an 18-mesh screen with no agglomeration. The average weights of coated pellets filled inside of capsules were monitored during the filling process. A simple liquid chromatographic method was developed and validated for the assay and uniformity test of procaterol HCl in different dosage forms. The results of assay and content uniformity test for both in-house product and a commercial product, i.e., Meptin®-mini tablet, were satisfied. The data of f₂ function and ANOVA analysis for the dissolution profiles of both procaterol HCl products suggested that they are pharmaceutical equivalent.

In an in vivo study (n = 24), a single dose of 75 µg procaterol HCl was administrated to each volunteer and the plasma concentration of procaterol was determined by a LC/MS/MS method, developed by the same authors. There were no significant differences (p > 0.05) in the data of AUC_0→16h, AUC_0→∞, C_max, and MRT for both preparations. It is confirmed that the pellets capsule produced in this study is bioequivalent with Meptin®-mini tablet.     

A New Rapidly Absorbed Paracetamol Tablet Containing Sodium Bicarbonate. II. Dissolution Studies and In Vitro/In Vivo Correlation

ABSTRACT

The objective of this study was to compare the in vitro dissolution profile of a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with that of a conventional paracetamol tablet (P), and to relate these by deconvolution and mapping to in vivo release. The dissolution methods used include the standard procedure described in the USP monograph for paracetamol tablets, employing buffer at pH 5.8 or 0.05 M HCl at stirrer speeds between 10 and 50 rpm. The mapping process was developed and implemented in Microsoft Excel® worksheets that iteratively calculated the optimal values of scale and shape factors which linked in vivo time to in vitro time. The in vitro–in vivo correlation (IVIVC) was carried out simultaneously for both formulations to produce common mapping factors. The USP method, using buffer at pH 5.8, demonstrated no difference between the two products. However, using an acidic medium the rate of dissolution of P but not of PS decreased with decreasing stirrer speed. A significant correlation (r = 0.773; p<.00001) was established between in vivo release and in vitro dissolution using the profiles obtained with 0.05 M HCl and a stirrer speed of 30 rpm. The scale factor for optimal simultaneous IVIVC in the fasting state was 2.54 and the shape factor was 0.16; corresponding values for mapping in the fed state were 3.37 and 0.13 (implying a larger in vitro–in vivo time difference but reduced shape difference in the fed state). The current IVIVC explains, in part, the observed in vivo variability of the two products. The approach to mapping may also be extended to different batches of these products, to predict the impact of any changes of in vitro dissolution on in vivo release and plasma drug concentration–time profiles.     

Design and In Vitro Evaluation of Polymeric Formulae of Simvastatin for Local Bone Induction

ABSTRACT

Simvastatin (SVS), a cholesterol-lowering drug, has been shown to stimulate bone formation. This study deals with the design and in vitro evaluation of local delivery systems for simvastatin. They are intended to treat bony defects resulting from periodontitis or to induce osteogenesis around the titanium implants. Granules and gels were formulated using bioerodible/biocompatible polymers, namely hydroxypropylmethyl cellulose (H), sodium carboxymethyl cellulose (C), and chitosan (Ch). The in vitro release profiles and kinetics were evaluated and the swelling and/or erosion was monitored. Differential scanning calorimetry (DSC) and infrared (IR) were used to detect any SVS/polymer interactions that may affect drug release. The results revealed variable extents of controlled drug release from the designed formulae depending on the polymer nature. About 50% cumulative SVS was released from both H granules and gel formulae within 24 h and ～66% and ～88% from C granules and gel, respectively. Ch formulae exhibited ～50% release from granules and ～30% from gel.     

肌细胞途径血友病B基因治疗高表达载体的构建及表达研究

构建了以ＭＣＫ（肌肉肌酸激酶）增强子增强、β－ａｃｔｉｎ启动子启动的、反向插入载体Ｇ１Ｎａ的Ｇ１ＮａＰＡＩＸｉ′ＢＡＭ。在与同一系列的、仅内含子元件有差异的载体Ｇ１ＮａＭＢＡＩＸ和Ｇ１ＮａＭＢＡｉＩＸ的体外体内表达比较证明，反向载体是表达最高最稳定的。进一步的二次体内注射研究表明，此载体是国内已报道的最适于肌细胞途径血友病Ｂ基因治疗的反转录病毒载体。     

In Vitro Release Studies of Piroxicam from Oil-in-Water Creams and Hydroalcoholic Gel Topical Formulations

The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37°C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.