The Influence of Various Dispersing Agents on the Dissolution Rate of Hydrochlorothiazide

Abstract

The solvent and melt methods were employed to prepare solid dispersions with various water soluble carriers and sparingly soluble drug, hydrochlorothiazide. The carriers investigated included dextrose, sorbitol, tartaric acid and urea. Dispersion with urea was superior to other carriers in releasing the drug into solution. Dextrose - melt showed decomposition of the drug. Sorbitol drug physical mixture produced a faster rate of dissolution of the drug than the melt dispersions. The eutectic mixture of urea and drug cooled at room temperature (28°) produced a faster dissolution rate of the drug than the mixture cooled at -2°.     

Influence of Sodium Caseinate on the Dissolution Rate of Hydrochlorothiazide and Chlorothiazide

Abstract

The solubility and dissolution characteristics of drug-casein systems were investigated and their solid state properties examined. Systems of varying drug-sodium caseinate weight fraction were prepared by physical mixing and freeze drying. Enhancements in the intrinsic dissolution rates were obtained for freeze dried systems of both drugs. The relative enhancement for 50/50 systems in phosphate buffer pH 7.4 was 5 fold and 1.5 fold for chlorothiazide and hydrochlorothiazide respectively. A 35 fold increase was observed for the chlorothiazide system in water, The release of both drugs from mechanically mixed systems in phosphate buffer approximated to a non interacting model, while release from hydrochlorothiazide systems in 0.1N HC1 showed a tendency towards matrix controlled release. Thus the magnitude of the effect is dependant on the nature of the drug, the content of carrier, the method of preparation and the dissolution medium.     

Influence of Sodium Caseinate on the Dissolution Rate of Hydrochlorothiazide and Chlorothiazide

The solubility and dissolution characteristics of drug-casein systems were investigated and their solid state properties examined. Systems of varying drug-sodium caseinate weight fraction were prepared by physical mixing and freeze drying. Enhancements in the intrinsic dissolution rates were obtained for freeze dried systems of both drugs. The relative enhancement for 50/50 systems in phosphate buffer pH 7.4 was 5 fold and 1.5 fold for chlorothiazide and hydrochlorothiazide respectively. A 35 fold increase was observed for the chlorothiazide system in water, The release of both drugs from mechanically mixed systems in phosphate buffer approximated to a non interacting model, while release from hydrochlorothiazide systems in 0.1N HC1 showed a tendency towards matrix controlled release. Thus the magnitude of the effect is dependant on the nature of the drug, the content of carrier, the method of preparation and the dissolution medium.     

The Influence of Various Dispersion Methods on the Rate of Dissolution of Sulfabenzamide

Abstract

The solvent and melt methods were employed to prepare solid dispersions with various water soluble carriers and a slightly soluble drug, sulfabenzamide. The carriers investigated included citric acid, succinic acid, dextrose, polyethylene glycol 6000, mannitol and urea. Dispersions with dextrose were superior to other carriers in releasing the drug into solution. Melts with both dextrose and urea produced faster rates of dissolution of sulfabenzamide than the coprecipitates from the solvent method. With mannitol and polyethylene glycol 6000, the coprecipitates produced a faster rate of dissolution of the drug than the melt dispersions.     

Dissolution Rate and Bioavailability of Spironolactone Tablets: Effect of Various Technological Factors

The effects of the magnesium stearate, talc and gelatin contents of spironolactone tablets on dissolution rate and bioavailability of the drug have been evaluated. The dissolution test results for eight formulations corresponding to a 2×2×2 factorial design showed dissolution rates to be chiefly dependent on gelatin content. Testing the bioavailability of the eight formulations using a balanced incomplete block design revealed no evidence of bioinequivalence, but in view of the possibility that the absence of significant differences had been due to the large number of formulations (and consequent lack of sensitivity on the part of experimental design) three representative formulations were re-tested using a 3×3 Latin square design. The results confirmed those of the balanced incomplete block study. Use of the balanced incomplete block design is advocated for bioavailability studies in which a large number of formulations are to be compared.     

Dissolution Rate and Bioavailability of Spironolactone Tablets: Effect of Various Technological Factors

Abstract

The effects of the magnesium stearate, talc and gelatin contents of spironolactone tablets on dissolution rate and bioavailability of the drug have been evaluated. The dissolution test results for eight formulations corresponding to a 2×2×2 factorial design showed dissolution rates to be chiefly dependent on gelatin content. Testing the bioavailability of the eight formulations using a balanced incomplete block design revealed no evidence of bioinequivalence, but in view of the possibility that the absence of significant differences had been due to the large number of formulations (and consequent lack of sensitivity on the part of experimental design) three representative formulations were re-tested using a 3×3 Latin square design. The results confirmed those of the balanced incomplete block study. Use of the balanced incomplete block design is advocated for bioavailability studies in which a large number of formulations are to be compared.     

Effect of Some Polymers on the Physico-Chemical and Dissolution Properties of Hydrochlorothiazide II

Different ratios of hydrochlorothiazide (HCT) and each of Polyethylene glycol (PEG) and B-cyclodextrin (B-CD) solid dispersions were prepared by melting and solvent method respectively. The solid dispersions were subjected to X-ray diffraction, I.R. spectroscopy, DSC and Dissolution from constant surface tablets. The drug was in the amorphous form when the ratios of the drug/PEG were less than 1:3. It formed hydrogen bond with both polymers. The dissolution of the drug from drug/PEG and drug/B-CD solid dispersions increased with the increase in the weight fraction of the polymers, reaching a maximum and then decreased with further increase of the latters.     

Effect of Some Polymers on the Physico-Chemical and Dissolution Properties of Hydrochlorothiazide II

Different ratios of hydrochlorothiazide (HCT) and each of Polyethylene glycol (PEG) and B-cyclodextrin (B-CD) solid dispersions were prepared by melting and solvent method respectively. The solid dispersions were subjected to X-ray diffraction, I.R. spectroscopy, DSC and Dissolution from constant surface tablets. The drug was in the amorphous form when the ratios of the drug/PEG were less than 1:3. It formed hydrogen bond with both polymers. The dissolution of the drug from drug/PEG and drug/B-CD solid dispersions increased with the increase in the weight fraction of the polymers, reaching a maximum and then decreased with further increase of the latters.     

采用双重分散剂制备水溶性超微纺锤形碳酸钙

首次报道了将未经消化的工业生石灰转化为CaCl2 ,对于反应中产生的氨不进行分离 ,直接作为后续反应的 pH调节剂及分散剂的前驱物 ,通过PAM和NH4 Cl双重分散剂作用下 ,制备水溶性超微纺锤形CaCO3 粉体的工艺过程 ,并对其反应过程、烘干条件进行了探讨 ,表征了CaCO3 的外貌 ,测定了粒度及粒度分布 ,并分析了纯度。结果表明 ,纺锤体长径比为 3 :1,粒度分布为 0 .1～ 0 .5 μm ,平均粒径为0 .2 4μm,纯度高于 99.90 %。     

The Wetting and Dissolution Rate of Phenobarbitone Powders

Abstract

The wetting of phenobarbitone powders by solutions of sodium lauryl sulphate has been measured. Large changes in contact angle and adhesion tension occur at low surfactant concentrations followed by more gradual changes at higher concentrations. The dissolution rates of phenobarbitone from capsules reflect these changes showing that initially, dissolution is penetration rate limited.     

The Wetting and Dissolution Rate of Phenobarbitone Powders

The wetting of phenobarbitone powders by solutions of sodium lauryl sulphate has been measured. Large changes in contact angle and adhesion tension occur at low surfactant concentrations followed by more gradual changes at higher concentrations. The dissolution rates of phenobarbitone from capsules reflect these changes showing that initially, dissolution is penetration rate limited.     

The Influence of Formulation on the Dissolution Profile of Diclofenac Sodium Tablets

ABSTRACT

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

Effect of Aging on the Dissolution Rate of Nalidixic Acid Tablets

Investigation of the dissolution rate profiles of nalidixic acid tablets of three commercial brands was carried out. Using the U.S.P. paddle method, significant inter-brand variations in dissolution rates were found and the tablets did not pass the U.S.P. dissolution test. The dissolution of the tablets was also found to be adversely affected on aging. The observed differences in dissolution rates of the tablets examined were unrelated to their disintegration times. An attempt was made to improve the dissolution rate of nalidixic acid tablets through hydrophilization of nalidixic acid powder and use of tablet excipients with high aqueous solubility were found to yield tablets of good physical qualities which were unaffected on aging.     

Effect of Aging on the Dissolution Rate of Nalidixic Acid Tablets

Abstract

Investigation of the dissolution rate profiles of nalidixic acid tablets of three commercial brands was carried out. Using the U.S.P. paddle method, significant inter-brand variations in dissolution rates were found and the tablets did not pass the U.S.P. dissolution test. The dissolution of the tablets was also found to be adversely affected on aging. The observed differences in dissolution rates of the tablets examined were unrelated to their disintegration times. An attempt was made to improve the dissolution rate of nalidixic acid tablets through hydrophilization of nalidixic acid powder and use of tablet excipients with high aqueous solubility were found to yield tablets of good physical qualities which were unaffected on aging.     

Solubility and Dissolution Rate of Progesterone-Cyclodextrin-Polymer Systems

ABSTRACT

This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl-β-CD (HPβ-CD), hydoxypropyl-γ-CD (HPγ-CD), permethyl-β-CD (PMβ-CD), and sulfobutylether-β-CD (SBEβ-CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. The results showed that HPβ-CD and PMβ-CD were the most efficient among the four cyclodextrins for the solubilization of progesterone, with the highest apparent stability constants. Therefore, dissolution studies were conducted on these latest progesterone/cyclodextrin complexes and physical mixtures. Two additional natural cyclodextrins, β-CD and γ-CD, were taken as references. Hence, the influence of more highly soluble derivatives of β‐CD (HPβ-CD, PMβ-CD) on the progesterone dissolution rate, in comparison to pristine β-CD, alongside an increase in the cavity width for γ-CD versus β-CD, were investigated. The dissolution kinetics of progesterone dissolved from HPβ-CD, PMβ-CD, and γ-CD revealed higher constant rates in comparison to β-CD. Therefore, the aim of the second part of this study was to investigate the possibility of improving the dissolution rate of progesterone/β-CD binary systems upon formation of ternary complexes with the hydrophilic polymer, PEG 6000, as β-CD had the smallest progesterone solubility and dissolution capacity among the four cyclodextrins studied (β‐CD, HPβ-CD, HPγ-CD and PMβ-CD). The results indicated that dissolution constant rates were considerably enhanced for the 5% and 10% progesterone/β-CD complexes in PEG 6000.

The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone β-cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.     

Studies of Furosemide Tablets II Influence of Wet-Mixing Time, Binder Volume and Batch Variation on Dissolution Rate

The effect of wet-mixing time and the volume of granulating solution on furosemide tablet quality and in vitro dissolution rate were studied. The wet-mixing time has shown an effect on the in vitro dissolution of furosemide tablet formulation. Small variations in wet-mixing time can be important and effective on the tablet dissolution. A decrease in the dissolution rate was observed when the time of wet-mixing increased.

Changes in the volume of granulating solution, when the amount of gelatin was constant, did not alter the tablet dissolution.

Moreover, the effect of batch variation on tablet formulation was also investigated. There was no significant differences in the dissolution of the different batch of furosemide bulk powder.     

Enhanced Solubility of Paracetamol by Various Hydrotropic Agents

The increase in the aqueous solubility of paracetamol by the use of various hydro tropes was studied.

These agents were sodium glycinate, sodium gentisate, sodium salicylate and nicotinamide. All of these agents increased the aqueous solubility to varying degrees, with nicotinamide and sodium salicylate being the most efficient solubilizers.

A conductance parameter was investigated as a mean of aiding interpretation of the solubility data. Dielectric constants could only be determined in the nicotinamide systems.

Ultra-violet spectral analysis, TLC, infra-red, and NMR techniques were utilized in order to elucidate the solubility mechanism. These tests indicate that no special bonding or complex formation exists for the sodium salt hydrotropes in these preliminary work. There is some evidence from UV & TLC analysis that nicotinamide and paracetamol enter into complex formation.

The other hydrotropic agents, in this study indicate the mechanism of solubilization is one of “salting - in” by causing miscibility of two formally immiscible liquid phases of ternary systems.     

Enhanced Solubility of Paracetamol by Various Hydrotropic Agents

Abstract

The increase in the aqueous solubility of paracetamol by the use of various hydro tropes was studied.

These agents were sodium glycinate, sodium gentisate, sodium salicylate and nicotinamide. All of these agents increased the aqueous solubility to varying degrees, with nicotinamide and sodium salicylate being the most efficient solubilizers.

A conductance parameter was investigated as a mean of aiding interpretation of the solubility data. Dielectric constants could only be determined in the nicotinamide systems.

Ultra-violet spectral analysis, TLC, infra-red, and NMR techniques were utilized in order to elucidate the solubility mechanism. These tests indicate that no special bonding or complex formation exists for the sodium salt hydrotropes in these preliminary work. There is some evidence from UV & TLC analysis that nicotinamide and paracetamol enter into complex formation.

The other hydrotropic agents, in this study indicate the mechanism of solubilization is one of “salting - in” by causing miscibility of two formally immiscible liquid phases of ternary systems.     

Influence of Montmorillonite on the Dissolution and Bioavailablity of Phenyton

The dissolution of phenytoin were studied from various phentyoin-montmorillonite combinations. Firstly, phentoin-montmorllionite combinations were obtained by precipitating phenytoin from two different solvents on to montmorillonite using drug to montmorillonite ratios. Secondly, physical mixtures of phenytoin and montmorillonite were prepared in were compressed into tablets and the dissolution rates were determined. The dissolution rates of phenytoin with the dissolution rates of the combinations. The montmorillonite increased the dissolution rate of phenyton from all the combinations to such an extent that the dissolution rates compressed well with those obtained form phenytoin sodium.

The bioavailability of phentyoin from three different phenytoin-montmorillonite mixutres were compared well the bioavailability from a phenytoin sodium capsule in four volunters. More phenytoin were absorbed from the phenytoin-montrillonite mixtures than from the phenytoin sodium. The absorption rate of phenytoin from the three different montmorillonite mixtures were fastef than from the phenytoin sodium capsule for the first hour, after administtration. After one hour the phenytoin blood levels from the phenytoin-montmorillonite mixtures started to level of to reach lower peak concentrations in plasma than that obtained from phenytoin-montmorillonite mixtures (1:1 and 1:9 ratios) was more than that absorbed form phenytoin sodium. The advantages of combining phenytoin and montmorillonite for the improvement of the bioavailability of phenytoin have clearly been demonstrated.