Studies on the Microencapsulation of Dextropropoxyphene Hydrochloride. Part 2. Tee in vivo Urinary Excretion in Man.

I this study, the spectrophotometric method suggested by Amundson et al (1) was used for the quantitation of dextropropoxyphene hydrochloride (D-PRX.HCL) (free drug plus metabolite) in urine after the oral administration of powder drug and microcaosules.     

Studies on the Microencapsulation of Dextropropoxyphene Hydrochloride. Part 2. Tee in vivo Urinary Excretion in Man.

Abstract

I this study, the spectrophotometric method suggested by Amundson et al (1) was used for the quantitation of dextropropoxyphene hydrochloride (D-PRX.HCL) (free drug plus metabolite) in urine after the oral administration of powder drug and microcaosules.     

Sustained-Release Dosage Form of Nicardipine Hydrochloride: Application of Factorial Design and Effect of Surfactant on Release Kinetics

Microcapsules of nicardipine hydrochloride with core:wall ratios of 1:1, 2:1, and 1:2 were prepared by the coacervation-phase separation method, using ethyl-cellulose as the coating material. Two batches of nicardipine hydrochloride microscapsules were divided into size fraction by using standard sieves ranging from 840 μm to 476 pn. Dissolution rate studies from microcapsules were performed using the USP XXII basket method. The kinetic model according to the Rosin-Rammler-Sperling-Bennet-Weibull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. Preparation and dissolution rate studies on the nicardipine hydrochloride microcapsules were pellformed and the influence of particle size, core:wall ratio, and the amount of nicardipine hydrochloride on the release rate was examined by 2³ factorial design. The sign@cance of the observed effects was tested with the F test. A surface active substance was added in the dissolution medium to understand how this substance effects the release of drug from ideal microcapsule form which is found by the findings of the 2³ factorial design. Dissolution studies were repeated with this ideal formulation using different ratio of Tween 20.

The results of this study suggested that the solubility and bioavailability of the sustained-release dosage forms of nicardipine hydrochloride using sullface active substances could be increased.     

An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel^® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Dsc Screening for Drug-Drug Interactions in Poly Pharmaceuticals Intended for the Alleviation of the Symptoms of Colds and Flu. II.

DSC screening for drug-drug interactions of a polypharmaceutical capsule dosage form containing salicylaminde, ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride was performed. The results show the following:

1. Ascorbic acid is incompatible with salicylamide, pyrilamine maleate and pheynylephrine hydrochloride.

2. Salicylamide is incompatible with ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride.

3. Pyrilamine maleate is incompatible with ascorbic acid, salicylamide and phenylephrine hydrochloride.

4. Phenylephrine hydrochloride is incompatible with salicylamide, pyrilamine maleate and ascorbic acid.     

Sustained-Release Dosage Form of Nicardipine Hydrochloride: Application of Factorial Design and Effect of Surfactant on Release Kinetics

Abstract

Microcapsules of nicardipine hydrochloride with core:wall ratios of 1:1, 2:1, and 1:2 were prepared by the coacervation-phase separation method, using ethyl-cellulose as the coating material. Two batches of nicardipine hydrochloride microscapsules were divided into size fraction by using standard sieves ranging from 840 μm to 476 pn. Dissolution rate studies from microcapsules were performed using the USP XXII basket method. The kinetic model according to the Rosin-Rammler-Sperling-Bennet-Weibull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. Preparation and dissolution rate studies on the nicardipine hydrochloride microcapsules were pellformed and the influence of particle size, core:wall ratio, and the amount of nicardipine hydrochloride on the release rate was examined by 2³ factorial design. The sign@cance of the observed effects was tested with the F test. A surface active substance was added in the dissolution medium to understand how this substance effects the release of drug from ideal microcapsule form which is found by the findings of the 2³ factorial design. Dissolution studies were repeated with this ideal formulation using different ratio of Tween 20.

The results of this study suggested that the solubility and bioavailability of the sustained-release dosage forms of nicardipine hydrochloride using sullface active substances could be increased.     

An In Vitro Evaluation of Fenugreek Mucilage as a Potential Excipient for Oral Controlled-Release Matrix Tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46–0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Crystal engineering to improve physicochemical properties of mefloquine hydrochloride

Background: Pharmaceutical cocrystallization is a promising alternative for improving the solubility and dissolution rate or manipulating other physical properties of active pharmaceutical ingredients. The objective of this investigation was to study the effect of cocrystallization with different cocrystal formers on physicochemical properties of mefloquine hydrochloride. Method: Cocrystals were prepared by solution crystallization method – mefloquine hydrochloride (414.8 mg, 1 mmol) and different cocrystal formers (1/2 mmol) were dissolved in 20 mL of ethanol with warming. Solution was cooled in ice bath for 6 hours. The crystals were isolated by filtration through a membrane (0.45 μm) and dried in the air. The pure drug and the prepared cocrystals were characterized in terms of saturation solubility, drug content, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, in vitro dissolution studies, and stability studies. Results: The cocrystals showed enhanced solubility and dissolution rate. The cocrystals were found to be stable over the period of 6 months confirmed from stability studies. Conclusion: Cocrystals resist the conversion of anhydrous form of drug into its hydrate which is responsible for the drugs less solubility and dissolution rate.     

Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof-of-concept clinical studies

Objective: A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug’s low solubility in water and to conduct proof-of-concept clinical studies.

Significance: Elacridar is highly demanded for proof-of-concept clinical trials that study the drug’s suitability to boost brain penetration and bioavailability of numerous anticancer agents. Previously, clinical trials with elacridar were performed with a tablet containing elacridar hydrochloride. However, this tablet formulation resulted in poor and unpredictable absorption which was caused by the low aqueous solubility of elacridar hydrochloride.

Methods: Twenty four different ASDs were produced and dissolution was compared to crystalline elacridar hydrochloride and a crystalline physical mixture. The formulation with highest dissolution was characterized for amorphicity. Subsequently, a tablet was developed and monitored for chemical/physical stability for 12 months at +15–25?°C, +2–8?°C and ?20?°C.

Results: The ASD powder was composed of freeze dried elacridar hydrochloride–povidone K30–sodium dodecyl sulfate (1:6:1, w/w/w), appeared fully amorphous and resulted in complete dissolution whereas crystalline elacridar hydrochloride resulted in only 1% dissolution. The ASD tablets contained 25?mg elacridar hydrochloride and were stable for at least 12 months at –20?°C.

Conclusions: The ASD tablet was considered feasible for proof-of-concept clinical studies and is now used as such.     

正交实验法研究液膜提取黄连素的最佳条件

对影响黄连素提取量的几个因素进行正交实验，结果表明在油内比等于：1.5，膜内HCl浓度为0.8mol\L，载体油酸用量为0.075mol\L，乳化剂Span-80用量为2.5%（质量分数）时，黄连素提取量可达总含量的75%以上。     

Dsc Screening for Drug-Drug Interactions in Poly Pharmaceuticals Intended for the Alleviation of the Symptoms of Colds and Flu. II.

Abstract

DSC screening for drug-drug interactions of a polypharmaceutical capsule dosage form containing salicylaminde, ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride was performed. The results show the following:

1. Ascorbic acid is incompatible with salicylamide, pyrilamine maleate and pheynylephrine hydrochloride.

2. Salicylamide is incompatible with ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride.

3. Pyrilamine maleate is incompatible with ascorbic acid, salicylamide and phenylephrine hydrochloride.

4. Phenylephrine hydrochloride is incompatible with salicylamide, pyrilamine maleate and ascorbic acid.     

ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜对樱桃的保鲜效果

目的研究ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜对樱桃的保鲜效果。方法以"美早"樱桃为保鲜对象,采用壳聚糖涂膜、ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜保鲜樱桃,以未涂膜处理的樱桃为空白对照,并用一次性打孔水果包装盒包装樱桃,研究冷藏贮藏期间不同处理组樱桃的主要品质指标随贮藏时间的变化情况。结果ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜在降低樱桃质量损失率、凹陷率、腐烂率等方面表现更佳;在贮藏6 d后,ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜处理组樱桃的可滴定酸质量分数为0.52%,Vc含量为59.5 mg/kg,与未涂膜的空白组樱桃相比,可以在一定程度上减缓樱桃中可滴定酸和Vc含量的降低;ε-聚赖氨酸盐酸盐/壳聚糖复合涂膜能够更好地改善贮藏期间樱桃的硬度和色泽。结论ε-聚赖氨酸盐酸盐可以与壳聚糖协同作用,对樱桃发挥更好的保鲜作用。     

Comparison of the Dissolution Characteristics of Long-Acting Quinacrine Hydrochloride Pellets Using Basket, Paddle and Continuous Flow Methods III

In this study the dissolution rate profiles of formulated long acting quinacrine hydrochloride pellets were investigated by using basket, paddle and continuous flow methods.

There was no significant difference observed between these dissolution profiles.     

Spectrophdtometric Determination of Hydralazine Hydrochloride, Oxprenolol Hydrochloride & Chlorthalidone in Combination and for Oxprenolol Hydrochloride as Single Component Dosage Form

Three component tablet assay and single component tablet assay are presented. The first is performed for hydralazine hydrochloride, oxprenolol hydrochloride & chlorthalidone existing in a ratio 2.5: 8: 1 respectively. Hydralazine is estimated through absorbance measurements at 314 nm, D₁ at 315 nm or D₂-at 316 nm. Modified Vierordts method-after absorbance correction from hydralazine hydrochloride interference and also D₂ methods are applied for oxprenolol hydrochloride assay. Chlorthalidone, the minor component, is assayed after its extraction using D₁ or D₂ measured at 282 nm & 268-284 nm respectively. For single tablet assay, oxprenolol hydrochloride is assayed using A_max at 272 nm, D₁-measurement at 252-274 nm & D₂-measurement at 260-278 nm. The first method is suffering from systematic error corrected by the latter two methods.     

Enhanced percutaneous permeability of nicardipine hydrochloride by carvone across the rat abdominal skin

The purpose of this study was to investigate the effect of carvone on the permeation of nicardipine hydrochloride across the excised rat abdominal epidermis from 2% w/w hydroxypropyl cellulose (HPC) gel system. The HPC gel formulations containing nicardipine hydrochloride (1% w/w) and selected concentrations of carvone (0 to 12% w/w) were prepared, and evaluated for drug content, stability of the drug, and in vitro permeation of the drug through excised rat abdominal epidermis. The HPC gel was found to contain 99.98 to 101.6% of nicardipine hydrochloride, and the drug was found to be stable in the HPC gels. The permeation flux of nicardipine hydrochloride across rat epidermis was increased markedly by the addition of carvone to the HPC gels. A maximum flux of nicardipine hydrochloride (243.95.70 ± 1.90 µg/cm²/hr) was observed with an enhancement ratio of 7.9 when carvone was incorporated at a concentration of 12% w/w in the HPC reservoir system. The differential scanning calorimetry and Fourier transform-infrared data indicated that carvone increased the permeability of nicardipine hydrochloride across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that carvone may be useful for enhancing the skin permeability of nicardipine hydrochloride from transdermal therapeutic system containing HPC gel as a reservoir.     

1mol/L HCl中不同浓度维生素B1和B6对碳钢的缓蚀性能及机理

通过研究盐酸硫胺(维生素B1),吡哆醇(维生素B6)作为缓独剂对碳钢的缓蚀行为及其作用机制,可为新型环境友好缓蚀剂的开发和应用提供一定的理论基础.利用失重法、极化曲线法和交流阻抗法、量子化学方法研究了不同浓度维生素B1和B6在1mol/L盐酸溶液中对Q235碳钢的缓蚀性能及机理.结果表明:碳钢的腐独速率随缓性剂浓度的增...     

Solubility and solution stability studies of different amino acid prodrugs of bromhexine

Objective: The aim of the present study was to prepare the amino acid prodrugs of bromhexine hydrochloride to improve its solubility. Methods: All the prodrugs were synthesized by first reacting bromhexine with tert-butoxycarbonyl (Boc) protected amino acid and then deprotection was carried out by using trifluoroacetic acid. These prodrugs were characterized by their melting points, NMR, mass and FTIR spectroscopy. Solubility and partition coefficient of bromhexine and various prodrugs were determined. The solution stability of various prodrugs was also determined in various buffers of pH ranging from 2 to 10. Degradation rate constants and half-life were also determined at various pH. Results and discussion: The structures of all the synthesized prodrugs were confirmed by NMR, mass and FTIR spectra. The prodrug 2-N-l-alanyl-bromhexine hydrochloride showed maximum solubility and minimum partition coefficient value. These prodrugs may hydrolyze by one or more mechanisms. The order of decreasing rates of hydrolysis was 2-N-l-prolyl-bromhexine hydrochloride > 2-N-glycyl-bromhexine hydrochloride > 2-N-l-alanyl-bromhexine hydrochloride. All the prodrugs exhibited maximum stability in the acidic pH range and undergo base catalyzed hydrolysis. Conclusion: Solubility studies and partition coefficient values indicated that the synthesized prodrug, 2-N-l-alanyl-bromhexine hydrochloride, was least lipophilic as compared to other synthesized prodrugs. Solution stability studies showed that this prodrug undergo minimum hydrolysis at 37°C. So, it is concluded that 2-N-l-alanyl-bromhexine hydrochloride exhibits better solubility and stability as compared to other synthesized prodrugs.     

Influence of Dissolution Medium Agitation on Release Profiles of Sustained-Release Tablets

Reaching nearly perfect sink conditions is very important in the determination of drug dissolution rates. Many times, the only factor that is taken into consideration in achieving sink conditions is the relation between the drug concentration and its solubility. The analytical conditions of the dissolution assay, as well as the dissolution apparatus, stirring speed, and nature and volume of the dissolution fluid may also influence the dissolution results. The main objective of this work was to study the influence of the stirring rate conditions and of the dissolution apparatus in the diltiazem hydrochloride release from tablets. Diltiazem hydrochloride sustained-release (SR) tablets were tested and the following dissolution parameters were evaluated: t_10%, t_25%, t_50%, dissolution time, mean dissolution time (MDT), and dissolution efficiency (DE) at t₁₂₀, and at t₃₆₀. To analyze the release mechanism, several release models were tested, such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull, and Korsmeyer-Peppas. The similarities between two in vitro dissolution profiles were assessed by the similarity factor f₂. The in vitro release kinetics of diltiazem hydrochloride sustained-release tablets were evaluated using the USP 2 (paddle) and USP 4 (flow-through) apparatus.     

Preparation and in vivo evaluation of spray dried matrix type controlled-release microparticles of tamsulosin hydrochloride for orally disintegrating tablet

The objective of this study was to achieve an optimal formulation of spray dried matrix type controlled-release (MTCR) microparticles containing tamsulosin hydrochloride for orally disintegrating tablet. To control the release rate of tamsulosin hydrochloride, Acrylate-methacrylate copolymer (Eudragit(?) L-100 or Eudragit(?) S-100) and ethylcellulose were employed on the composition of MTCR microparticles. Physicochemical properties of MTCR microparticles such as particle size and SEM were characterized. Pharmacokinetic parameters of tamsulosin hydrochloride were evaluated in the rats after oral administration. MTCR microparticles were spherical microparticles of around 10 μm diameter with a corrugated surface. ODTs containing MTCR microparticles were disintegrated within 30 s and MTCR microparticles were able to control the release rate of tamsulosin hydrochloride following Fickian diffusion mechanism. The in vitro release rates of tamsulosin hydrochloride from MTCR microparticles were proportional to the ratio of Acrylate-methacrylate copolymer to ethylcellulose. Moreover, MTCR microparticles retarded the in vivo release rate of tamsulosin hydrochloride without reducing the bioavailability. Our results suggest that MTCR microparticles may be potential oral dosage forms to control the release and to improve the bioavailability of tamsulosin hydrochloride.     

High Performance Liquid Chromatographic Analysis and Dissolution of Dextropropoxyphene Napsylate with other Analgesics in Capsule Formulations

A reversed phase high-performance liquid chromatographic method was developed for simultaneous quantitation of dextropropoxyphene napsylate in three different formulations. The first contains caffeine and aspirin while the others are combinations with acetaminophene. The mobile phase consisted of acetonitrile (30%) in acetate buffer. The assay was carried at 28Onm wavelength. The method is precise and does not require sample manipulation prior to analysis. The applicability of the assay procedure in studying dissolution rate of capsule formulations is described.