Dissolution system for Nifedipine Sustained Release Formulations

Abstract

An in-vitro system for evaluating Nifedipine sustained release formulations has been developed. Two systems were evaluated to simulate sink conditions and correlate the system with flow through dissolution system in mechanism. For the purpose of evaluation two commercial brands were studied. The acidic biphasic system was found to be good for in-vitro dissolution rate evaluation of sustained release nifedipine tablets. It can be successfully utilized for routine quality control work.     

Dissolution system for Nifedipine Sustained Release Formulations

An in-vitro system for evaluating Nifedipine sustained release formulations has been developed. Two systems were evaluated to simulate sink conditions and correlate the system with flow through dissolution system in mechanism. For the purpose of evaluation two commercial brands were studied. The acidic biphasic system was found to be good for in-vitro dissolution rate evaluation of sustained release nifedipine tablets. It can be successfully utilized for routine quality control work.     

Dissolution System for Nifedipine Sustained Release Formulations

An in-vitro system for evaluating Nifedipine sustained release formulations has been developed. Two systems were evaluated to simulate sink conditions and correlate the system with flow through dissolution system in mechanism. For the purpose of evaluation two commercial brands were studied. The acidic biphasic system was found to be good for in-vitro dissolution rate evaluation of sustained release nifedipine tablets. It can be successfully utilized for routine quality control work.     

A Flow-Through Dissolution Approach to In Vivo/In Vitro Correlation of Adinazolam Release from Sustained Release Formulations

Abstract

A Copley? fraction collector and a Disotest? flow-through system were coupled to provide an automatic discrete sampling flow-through dissolution system for use both in the “open-loop” and “closed-loop” mode. The system was used to investigate the release characteristics of adinazolam in sustained release formulations using a pH 1.2 simulated gastric fluid (without enzymes) dissolution medium (USP XXI). These experimental formulations are designed to provide relatively slow to rapid drug release. The dissolution effluent was analysed off-line by reverse phase HPLC to determine the adinazolam concentration at programmed timed intervals. The differential dissolution profiles produced when the system is used in the “open-loop” configuration are more discriminating in describing the release characteristics of the formulations according to the relative release rates than the “closed-loop” cumulative profiles. Using the characteristic dissolution time parameter from the Weibull function, a better correlation with in vivo bioavailability data was achieved for the data from the system in the “open-loop” mode than when it was used in the “closed-loop” mode. In the “open-loop” mode the Weibull function characteristic dissolution time parameter yielded the best quantitative correlation with a correlation coefficient of 0.92 compared to a value of 0.85 for the “closed-loop” configuration     

A Flow-Through Dissolution Approach to In Vivo/In Vitro Correlation of Adinazolam Release from Sustained Release Formulations

A Copley^TM fraction collector and a Disotest^TM flow-through system were coupled to provide an automatic discrete sampling flow-through dissolution system for use both in the “open-loop” and “closed-loop” mode. The system was used to investigate the release characteristics of adinazolam in sustained release formulations using a pH 1.2 simulated gastric fluid (without enzymes) dissolution medium (USP XXI). These experimental formulations are designed to provide relatively slow to rapid drug release. The dissolution effluent was analysed off-line by reverse phase HPLC to determine the adinazolam concentration at programmed timed intervals. The differential dissolution profiles produced when the system is used in the “open-loop” configuration are more discriminating in describing the release characteristics of the formulations according to the relative release rates than the “closed-loop” cumulative profiles. Using the characteristic dissolution time parameter from the Weibull function, a better correlation with in vivo bioavailability data was achieved for the data from the system in the “open-loop” mode than when it was used in the “closed-loop” mode. In the “open-loop” mode the Weibull function characteristic dissolution time parameter yielded the best quantitative correlation with a correlation coefficient of 0.92 compared to a value of 0.85 for the “closed-loop” configuration     

Multivariate Analysis of Variance of Dissolution Data in the Development of Oral Sustained Release Formulations

A multivariate analysis of variance applied to polinomial interpretation of growth curves in used for the interpretation of dissolution curves of four experimental, sustained release, wax type theophylline tablets.

The factors under study were glyceril palmitic stearate, carboxypol imethylene contents and compression force. The tablets were formulated according an experimental design based on 4 × 4 Hadamard matrix. The USP type I apparatus for dissolution test and CHI 0.1 N plus O.1%. polysorbate 80 as dissolution medium was used.

The statistical interpretation of results showed: first, that dissolution rates were almost constant for the four formulations during 8 h; second, the main difference between formulation dissolution rates can be inputed to fat excipient content and in much lesser extent to carboxipolymethylene content; third, the theopylline release rate was unaffected by compression force.     

Multivariate Analysis of Variance of Dissolution Data in the Development of Oral Sustained Release Formulations

Abstract

A multivariate analysis of variance applied to polinomial interpretation of growth curves in used for the interpretation of dissolution curves of four experimental, sustained release, wax type theophylline tablets.

The factors under study were glyceril palmitic stearate, carboxypol imethylene contents and compression force. The tablets were formulated according an experimental design based on 4 × 4 Hadamard matrix. The USP type I apparatus for dissolution test and CHI 0.1 N plus O.1%. polysorbate 80 as dissolution medium was used.

The statistical interpretation of results showed: first, that dissolution rates were almost constant for the four formulations during 8 h; second, the main difference between formulation dissolution rates can be inputed to fat excipient content and in much lesser extent to carboxipolymethylene content; third, the theopylline release rate was unaffected by compression force.     

Soft Gelatin Capsules Iii: An Accelerated Method for Evaluating the Dissolution Stability of Various Gel Formulations

A rapid method has been developed for the evaluation of the dissolution stability of various preformulation gels. Freshly prepared gel samples, after proper drying, were stored over a drying agent at above room temperatures. Periodically the dissolution of a stability sample in % dissolved for a given time was determined spectrophotometrically. In this manner, various preformulation gels could be evaluated in a relatively short time by changes in their dissolution rates from a slope values versus time plot for a given storage condition. Other applications of the method were in screening various plasticizers and additives for their solubility enhancing or protective properties.     

Soft Gelatin Capsules Iii: An Accelerated Method for Evaluating the Dissolution Stability of Various Gel Formulations

Abstract

A rapid method has been developed for the evaluation of the dissolution stability of various preformulation gels. Freshly prepared gel samples, after proper drying, were stored over a drying agent at above room temperatures. Periodically the dissolution of a stability sample in % dissolved for a given time was determined spectrophotometrically. In this manner, various preformulation gels could be evaluated in a relatively short time by changes in their dissolution rates from a slope values versus time plot for a given storage condition. Other applications of the method were in screening various plasticizers and additives for their solubility enhancing or protective properties.     

Evaluation of a Modified Paddle Method for Dissolution Testing

Abstract

A modification of the U.S.P. paddle method for dissolution was evaluated. A 10-mesh size circular stainless steel screen was placed at the bottom of the dissolution vessel establishing an elevated platform for the tablet. The modified method was compared with the U.S.P. paddle and basket methods utilizing three different tablet formulations of the nondisintigratiny type. Two tablet formulations contained a gel forming material hydroxypro-pylmethylcellulose K-4000 and the third tablet formulation has tricalcium phosphate as the major filler. The active ingredients were either dyphylline or melperone HCl. The data were evaluated by a one-way analysis of variance combined with Ryan-Einot-Gabriel-Welsch multiple F-test for comparison between methods. The results suggest that the proposed modified paddle method for dissolution may provide the formulator with an alternative for evaluating release of drugs from solid dosage forms containing swell able gums. This method offers the advantages of continuous visual monitoring of the dosage form to ascertain its integrity and full exposure of the total surface area of the tablet without sticking to the walls of the dissolution vessel     

Evaluation of a Modified Paddle Method for Dissolution Testing

A modification of the U.S.P. paddle method for dissolution was evaluated. A 10-mesh size circular stainless steel screen was placed at the bottom of the dissolution vessel establishing an elevated platform for the tablet. The modified method was compared with the U.S.P. paddle and basket methods utilizing three different tablet formulations of the nondisintigratiny type. Two tablet formulations contained a gel forming material hydroxypro-pylmethylcellulose K-4000 and the third tablet formulation has tricalcium phosphate as the major filler. The active ingredients were either dyphylline or melperone HCl. The data were evaluated by a one-way analysis of variance combined with Ryan-Einot-Gabriel-Welsch multiple F-test for comparison between methods. The results suggest that the proposed modified paddle method for dissolution may provide the formulator with an alternative for evaluating release of drugs from solid dosage forms containing swell able gums. This method offers the advantages of continuous visual monitoring of the dosage form to ascertain its integrity and full exposure of the total surface area of the tablet without sticking to the walls of the dissolution vessel     

Investigation of Dissolution Enhancement of Nifedipine by Deposition on Superdisintegrants

In this study we aimed to investigate the dissolution enhancement of nifedipine by the solvent deposition technique using superdisintegrants including Ac-Di-Sol, Kollldon CL, and Explotab as excipients. The relative significance of action of solvent deposition (deposition of small drug particles on the excipient after solvent is evaporated) and action of superdislntegrant was investigated. The effect of solvent on dissolution of nifedipine in the solvent deposition system was also Investigated. Differential scanning calorlmetry (DSC) was used to study the interaction between nifedipine and superdisintegrants. Capsules and tablets of a physical mixture and a solvent deposition system of nifedipine were prepared. The dissolution rate of nifedipine of these capsules and tablets was studied. The results of this study show that solvent deposition system with lactose and super dlslntegrants in capsule and tablet dosage forms can significantly enhance dissolution rate of nifedipine. Both the action of superdislntegrant and solvent deposition contribute to the enhancement of the dissolution, but the solvent deposition is mainly responsible for this enhancement. The solvent and disintegrants used can influence the dissolution rate also. The solvent deposition system using both Kollldon CL as excipient and dichloromethane as solvent has the highest dissolution rate. DSC study indicated Kollldon CL has the strongest interaction with nifedipine also.     

Improving the Dissolution and Bioavailability of Nifedipine Using Solid Dispersions and Solubilizers

ABSTRACT

Nifedipine (NF) is a poorly water-soluble drug, of low and irregular bioavailability after oral administration. Although some reports have attempted to improve the dissolution of NF using solid dispersions and solubilizers, little literature information is available on the in vivo performance of such preparations. The aim of the present work was to improve the therapeutic efficacy of NF via incorporation into different types of carriers, and to investigate their in vitro dissolution and bioavailability in rabbits. Nifedipine solid dispersions were prepared by fusion, solvent, and freeze-drying methods with polyethylene glycol (PEG) 6000 and PEG monomethylether 5000 (PEG MME 5000). Complexation of NF with β-cyclodextrin (β-CyD) and solubilization by sodium lauryl sulfate (SLS) have also been studied. The dissolution was determined by the flow-through cell in order to maintain perfect sink conditions. The solid dispersions resulted in a significant increase in the dissolution rate as compared to pure drug. The highest NF dissolution rate was obtained from solid dispersions containing 95% PEG 6000 prepared by the solvent method. While, unexpectedly, the highest absorption in rabbits was obtained from 95% PEG 6000 prepared by the fusion method. Compared to SLS, β-CyD gave higher in vitro and in vivo values. Differential scanning calorimetry (DSC) and powder x-ray diffractometry indicated that NF in solid dispersions is homogeneously distributed, and no drug crystallized out of the system. The DSC thermograms of NF-β-CyD complex and NF/SLS solid mixture showed a decrease in the NF endothermic peak. The x-rays showed different diffraction patterns of pure NF and pure carrier, suggesting the formation of a new solid form.     

Evaluation of an in Vitro Dissolution and Permeation Apparatus for Oral Solid Pharmaceutical Dosage Forms

An apparatus based in the USP dissolution test, the F-C-SL apparatus (Ferreira-Costa-Sousa Lobo), was developed that allowed the simultaneous evaluation of the in vitro release and permeation of oral solid pharmaceutical dosage forms. The release rate in both dissolution devices (USP and F-C-SL apparatus) was evaluated with acetaminophen tablets. Different test conditions (stirring rate and solvent volume ratio) were investigated and no significant differences in acetaminophen release rate were found between these apparatuses. In the F-C-SL apparatus, the in vitro permeation kinetics of acetaminophen were evaluated using synthetic membranes and followed a zero-order kinetic.     

Development of Controlled Release Formulations of Ketoprofen for Oral Use

Microencapsulated forms of ketoprofen were formulated using polymers and polymer combinations and their in-vitro release characteristics were evaluated against pure ketoprofen using Vanderkamp 600 dissolution test apparatus. Suspensions of cellulose acetate phthalate were prepared and various quantities of drug, glycerin, tween 80, span 80, methocel and avicel were added and the resulting solution was passed through a peristaltic pump into a hardening solution. Beads were formed, dried and the release of the drug was studied at various time intervals in a dissolution medium of simulated intestinal pH. The dissolution studies of the ketoprofen demonstrated differences in drug release properties depending on composition and method of preparation. A formulation of Methocel beads with equal proportions of the two surfactants released its drug content over a period of 12 hours in a zero-order fashion. Rapid drug dissolution was seen when the formulations contained Tween 80 as a surfactant. Varying the drug to CAP ratio in the suspension from 0.1 to 0.4 did not appear to alter dissolution. It is concluded that proper control of the formulation can give any desirable release from ketoprofen formulations.     

Modified Dissolution Method for Rifampin

It is important for any method of analysis to be acceptable carrying out in-vitro dissolution assays on capsules containing rifampin, using literature methods ^1,2 we obtained results which suggested tyhat rivfampin may be degrading during the procedure Therefore, we decided to investigate this problem.     

In Situ Gelling Pectin Formulations for Oral Sustained Delivery of Paracetamol

The purpose of this study was to evaluate the potential of a pectin formulation with in situ gelling properties for the oral sustained delivery of paracetamol (acetaminophen). The formulations consisted of dilute aqueous solutions (1% to 2% w/v) of low methoxy pectin containing calcium ions in complexed form, which on release in the acidic environment of the stomach caused gelation of the pectin. In vitro studies demonstrated diffusion‐controlled release of paracetamol from the gels over a period of 6 h. A bioavailability of approximately 96% of that of a paracetamol solution could be achieved from gels containing an identical dose of drug formed in situ in the stomachs of rats, with appreciably lower peak plasma levels and a sustained release of drug over a period of at least 6 h.     

Automated Dissolution Testing with Flow-Injection Analysis. Dissolution Profiles for the Antiviral Drugs, Dhpg and Acyclovir, in Capsule Formulations.

We have designed, assembled, and tested an automatic dissolution apparatus using flow-injection analysis (FIA) techniques with spectrophotometric detection. The components (pumps, switching valves, detector, and so forth) that comprise the system are all readily-available items used primarily for high-performance liquid chromatography. The system performs well as evidenced by the usual tests for precision, response linearity, and dissolution behavior of standard U.S.P. calibrator (salicylic acid and prednisone) tablets, and offers siqnificant advantages over conventional continuous-flow dissolution testing methods with respect to simplicity, cost, and versatility. Dissolution tests on capsules of the antiviral drugs, DHPG and acyclovir, showed very similar drug release profiles for both formulations.     

Evaluation of the Flow-Through Cell Dissolution Apparatus: Effects of Flow Rate, Glass Beads and Tablet Position on Drug Release from Different Type of Tablets

Several factors affecting the dissolution performance of various solid dosage forms tested using the flow-through cell method have been evaluated in this study. These factors include the flow rate, the position of tablets in the flow through cell and the glass beads, as well as the physical properties of the dosage forms. The experimental results indicated that the flow rate through the cell greatly affects drug release from disintegrating tablets. Drug release increases with increasing the flow rate of the dissolution medium, as expected. However, the flow rate does not significantly influence drug release from tablets which are not disintegratable, for example, an erodible tablet. The position of the tablets in the flow cell without glass beads is also of importance. Drug release from horizontally positioned tablets is different from vertically positioned tablets in the flow-through cell. It was also observed that the use of glass beads in the flow cell can make the flow pattern more laminar. This may help avoid a turbulent agitation within the cell, which could impact on drug dissolution.     

Evaluation of the Flow-Through Cell Dissolution Apparatus: Effects of Flow Rate,Glass Beads and Tablet Position on Drug Release from Different Type of Tablets

Abstract

Several factors affecting the dissolution performance of various solid dosage forms tested using the flow-through cell method have been evaluated in this study. These factors include the flow rate, the position of tablets in the flow through cell and the glass beads, as well as the physical properties of the dosage forms. The experimental results indicated that the flow rate through the cell greatly affects drug release from disintegrating tablets. Drug release increases with increasing the flow rate of the dissolution medium, as expected. However, the flow rate does not significantly influence drug release from tablets which are not disintegratable, for example, an erodible tablet. The position of the tablets in the flow cell without glass beads is also of importance. Drug release from horizontally positioned tablets is different from vertically positioned tablets in the flow-through cell. It was also observed that the use of glass beads in the flow cell can make the flow pattern more laminar. This may help avoid a turbulent agitation within the cell, which could impact on drug dissolution.