Improved Dissolution Rate of Poorly Soluble Drug by Incorporation of Buffers

This study focused on comparing dissolution rates of indomethacin after cocompressing with three different buffers (calcium carbonate, sodium carbonate, and sodium citrate) at pH 2 and 7. Factors affecting the dissolution rate were also examined, such as type and particle size of buffer and weight-to-weight ratio of drug to buffer. It was found that, at pH 7, the release rates of indomethacin with sodium carbonate (<74 μm, all proportions) and sodium citrate (<74 μm, 75% loading) at a 20-min test time were about 10-fold and 6-fold greater, respectively, than that of indomethacin alone. When the drug and buffer were compressed into tablets using a tableting machine, the release rates of indomethacin for the control, sodium carbonate incorporated (25% and 75% buffer loading), and sodium citrate incorporated (75% buffer loading) at a 15-min test time were 50%, 90%, 66%, and 67%, respectively.     

Development of a Clinical Capsule Formulation Containing a Marginally Water Soluble Drug

A good clinical development program maximizes the clinical efficacy of a new drug product and, in addition, requires only minimal formulation changes in the transition from clinical to market image product. This study demonstrates the development design as well as the technology utilized to improve the dissolution characteristics of a marginally water soluble drug to be administered in a capsule dosage form for clinical trials. A satisfactory formulation was achieved by controlling drug particle size, selecting an appropriate diluent and incorporating a surfactant.     

Development of a Clinical Capsule Formulation Containing a Marginally Water Soluble Drug

Abstract

A good clinical development program maximizes the clinical efficacy of a new drug product and, in addition, requires only minimal formulation changes in the transition from clinical to market image product. This study demonstrates the development design as well as the technology utilized to improve the dissolution characteristics of a marginally water soluble drug to be administered in a capsule dosage form for clinical trials. A satisfactory formulation was achieved by controlling drug particle size, selecting an appropriate diluent and incorporating a surfactant.     

Development and Validation of a Drug Release Rate Method for a Water Soluble Drug in a Liposome Preparation

Abstract

An in vitro method was developed to determine the rate of drug release from a liposome preparation. Three batches of liposomes containing orciprenaline sulphate were evaluated for release of drug over a 24 hour period in an end-over-end tumbler device. Intra and inter day precision studies indicate good reproducibility for this test method. This method is easy to use in drug development and quality control laboratories to evaluate drug release from liposome formulations.     

Development and Validation of a Drug Release Rate Method for a Water Soluble Drug in a Liposome Preparation

An in vitro method was developed to determine the rate of drug release from a liposome preparation. Three batches of liposomes containing orciprenaline sulphate were evaluated for release of drug over a 24 hour period in an end-over-end tumbler device. Intra and inter day precision studies indicate good reproducibility for this test method. This method is easy to use in drug development and quality control laboratories to evaluate drug release from liposome formulations.     

Nanoparticle Engineering Processes for Enhancing the Dissolution Rates of Poorly Water Soluble Drugs

Poor water solubility is an industry wide issue, especially for pharmaceutical scientists in drug discovery and drug development. In recent years, nanoparticle engineering processes have become promising approaches for the enhancement of dissolution rates of poorly water soluble drugs. Nanoparticle engineering enables manufacturing of poorly water soluble drugs into nanoparticles alone, or incorporation with a combination of pharmaceutical excipients. The use of these processes has dramatically improved in vitro dissolution rates and in vivo bioavailabilities of many poorly water soluble drugs. This review highlights several commercially or potentially commercially available nanoparticle engineering processes recently reported in the literature for increasing the dissolution properties of poorly water soluble drugs.     

Encapsulation of a Water Soluble Drug in a Liposome Preparation: Removal of Free Drug by Washing

Multilamellar and unilamellar vesicles were generated by using phosphatidylcholine-phosphatidylglycerol-cholesterol formulation. Liposomes were washed with normal saline to remove non-encapsulated drug. The result of the washing technique was the removal of free (non-encapsulated) drug, in turn improved the percent drug encapsulation in washed liposome preparation. Liposome vesicles were characterized by size, lamellarity, and percent drug encapsulation. Vesicle size was assessed by light scattering, lamellarity by electron microscopy and drug concentration by HPLC techniques.     

Dissolution, Bioavailability and Ulcerogenic Studies on Solid Dispersions of Indomethacin in Water Soluble Cellulose Polymers

The dissolution rate, bioavailability and ulcerogenic activity of indomethacin dispersed in water soluble cellulose polymers was investigated. Solid dispersions of indomethacin in hydroxypropyl cellulose-SL (HPC-SL), hydroxypropylmethyl cellulose (HPMC) and hydroxyethyl cellulose (HEC) were prepared by common solvent method with a view to improve its dissolution and absorption characteristics. The dispersions were evaluated by X-ray diffraction, TLC, IR, dissolution rate, bioavailability and ulcerogenic studies. TLC and IR studies indicated no interaction between indomethacin and carriers. Indomethacin in the dispersions was found to be in amorphous form. Marked increase in the dissolution rate and efficiency of indomethacin was observed in the case of solid dispersions. HPC-SL gave the highest dissolution improvement. A 30-fold increase in dissolution was observed with indomethacin-HPC-SL (9:1) dispersion.

In vivo studies in human subjects showed a significant increase in absorption rate (k_a) and serum levels of indomethacin with solid dispersions when compared to indomethacin alone. However, the extent of bioavailabilty was the same with both indomethacin and its solid dispersions. About 70-80 per cent reduction in ulcerogenic activity was observed with solid dispersions and the dispersions were found to have negligible ulcerogenic activity.     

Increasing Dissolution Rates of Poorly Soluble Drugs by Adsorption to Montnorillonith

The surface adsorption of griseofulvin, indomethacin and prednisone to colloidal magnesium aluminum silicate was shown to markedly improve the dissolution rates of there hydrophobic and party soluble drugs. The rapid release of drug from the surface of the clay was due to the weak physical bonding between the two materials and to the swelling of the clay in aqueous media. The hydrophilic and swelling properties of the montmorillonite clay in aqueous media also helped to facilitate the wetting of hydro-phobic drug substances. The equilibrating solvents employed in the preparation of the griseofulvin-clay adsorbates caused a significant variance in the dissolution profiles of griseofulvin. This did not occur with indomethacin. Dramatic increases in dissolution rates were seen with the prednisone adsorbates and 100 percent of the drug was present in solution from the 1:4 ad-sorbate after four minutes.     

The Effect of Nonionic Water Soluble Cellulose Polymers on the Settling of Drug Particles

Abstract

The influence of nonionic water soluble cellulose polymers, hydroxypropylmethylcellulose and hydroxyethylcellulose, on the settling of ibuprofen particles and the sediment behavior has been investigated. Results for hydroxypropylmethylcellulose systems showed that the higher the viscosity of the medium the slower the particle settling velocity. Heavily caked suspensions were obtained after particles settling. It was probably due to the gel network formation in the sediment.     

Drug Dissolution Testing: Today and Tomorrow

Abstract

This article discusses the present role of dissolution tests both in terms of current compendial requirements and the use of such tests by the pharmaceutical industry.

Insofar as future use is concerned, the suggestion is made that the compendia clearly distinguish between those monographs where dissolution tests have been shown to be of biological significance (i.e., Digoxin Tablets) and those which are simply acting as physical quality control procedures. Logically, a dissolution test should be applied to all solid dosage forms, although from a logistical point of view it might be appropriate to confine this requirement, at least initially, to those drugs having an aqueous solubility of 0.5 per cent or less.

In the future, the pharmaceutical industry should expand its use of dissolution testing both in formulation development and production control, with a view to establishing, in as many instances as possible, dissolution tests having biological significance, i.e., where reliable in vitro - in vivo correlations have been established.     

Drug Dissolution Testing: Today and Tomorrow

This article discusses the present role of dissolution tests both in terms of current compendial requirements and the use of such tests by the pharmaceutical industry.

Insofar as future use is concerned, the suggestion is made that the compendia clearly distinguish between those monographs where dissolution tests have been shown to be of biological significance (i.e., Digoxin Tablets) and those which are simply acting as physical quality control procedures. Logically, a dissolution test should be applied to all solid dosage forms, although from a logistical point of view it might be appropriate to confine this requirement, at least initially, to those drugs having an aqueous solubility of 0.5 per cent or less.

In the future, the pharmaceutical industry should expand its use of dissolution testing both in formulation development and production control, with a view to establishing, in as many instances as possible, dissolution tests having biological significance, i.e., where reliable in vitro - in vivo correlations have been established.     

Interpolymer Complexation and its Effect on Bioadhesive Strength 6 Dissolution Characteristics of Buccal Drug Delivery Systems

During the process of development of mucoadhesive buccal delivery systems, interpolymer complex formation between carboxy vinyl polymer, which is similar to polyacrylic acid and other polymers as hydroxypropyl cellulose, carbopol-934, sodium carboxymethyl cellulose and polyvinyl pyrrolidone was studied as a function of pH. It was observed that carbopol-934 shows strong complexation with polyvinyl pyrrolidone and hydroxypropyl cellulose, but very little with sodium carboxymethyl cellulose. The degree of complexation is higher at acidic pH and decreases with an increase in pH. In further studies, when mucoadhesive buccal tablets were prepared using these polymer combinations, it was observed that the degree of complexation between the two polymers affected the rate and extent of drug release and also the bioadhesive strength of the tablets.     

Preparation and Properties of a Novel Water Soluble Core Material

A novel water-soluble core material composed of polyethylene glycol, sodium chloride, mica powder and plasticizer was prepared. The compressive strength, bend strength, hygroscopic coefficient and the material solubility in water were investigated. The results show that the compressive yield strength of the soluble core can reach 1 MPa and the highest compressive strength can reach 4 MPa, the bend strength is as high as 6.65 MPa, the hygroscopic coefficient is lower than 0.22%/month and the solubility of suitable core material is 35.7-55.75 g/(min·m²). The wax pattern with undercuts was prepared successfully by using the novel water-soluble core material.     

Concept of Local Homogeneity of the Statistical Characteristics of Linear Systems and Its Relationship to Technical Fluctuations

The properties of conversion functions of linear systems are considered as random functions of information parameters and time. It is proved on the basis of performed experiments that conversion functions of linear systems are locally homogeneous random functions of the information parameters and possess stationary increments. There is shown to be a relationship between the static characteristics of the conversion functions and the characteristics of the internal noise of the systems considered.     

The Effect of the Wet Granulation Process on Drug Dissolution

Abstract

Wet granulation can be an important processing step for pharmaceutical solid dosage forms. In this investigation emphasis was directed towards the influence of a “simple” wet granulation process on drug release from granules and their resulting tablets. Direct compression blends of the same materials were used as controls. Binary mixtures containing a 5% level of either theophylline, hydrochlorothiazide or chlorpheniramine maleate in microcrystalline cellulose or lactose were granulated with water. Experimentally, the powders were dry blended in a planetary mixer, wet granulated, and subsequently wet milled and dried. No dry milling step was included. Granule characterization consisted of particle size, density, porosity, compression and dissolution testing. Dissolution results varied with the drug, as expected, and dissolution at 10 minutes ranged from 35 to 95 % release. In general, however, the results indicate that dissolution from granules and the corresponding direct compression blend are similar. Although differences in compressibility were observed in the systems studied, granulation was not found to be detrimental to drug release.     

转炉钢渣粉体的离子溶出与机理研究

采用一种新的循环抽提法对6种转炉钢渣粉体进行溶出性能测试,研究其溶出特性与溶出机理。结果表明:钢渣中Ca2+的溶出速率最大,Si4+次之,Al3+最小。钢渣粉体中各可溶性组分的溶出量与其原料中该组分质量分数之间并不存在显著的相关关系。钢渣粉体离子溶出速率可用简化动力学方程g(α)=Kt表示,其中Ca2+的溶出过程最符合由固膜扩散控制的缩芯模型特征,而Si4+、Al3+的溶出过程同时还与溶出界面上发生的化学反应有关。     

Measurement of the Surface Area Changes During the Dissolution of Poorly Soluble Drugs using a Wide Angle Photosedimentometer

Abstract

Using a Wide Angle Photosedimentometer, surface area changes during the dissolution of suspended particles of frusemide, glibenclamide and bendrofluazide have been measured. The method consisted of recording the change in optical density that occurs whilst the drugs are agitated in water in a 4cm square photosedimentometer cell. It was found that initially a high surface area was recorded which diminished exponentially with time and obeyed first order kinetics. From the surface area measurements, graphs of percentage drug dissolved against time were calculated and plotted and these profiles were found to correlate with similar plots of dissolution rate produced by analysing the amount dissolved spectrophotometrically. It was concluded that the surface area method offers an alternative technique for the measurement of the dissolution rate of poorly water soluble drugs, particularly when no adequate method exists for analysing the dissolved fraction.