Biomedical subjects

M C Gohel

Publications and source records attributed to M C Gohel.

10 recordsLinked to original sources

PubMed2005

A review of co-processed directly compressible excipients.

Direct compression is the preferred method for the preparation of tablets. The present review outlines the importance of the functionality of the directly compressible adjuvants in the formulation of tablets. The co-processing is the most widely explored method for the preparation of directly compressible adjuvants because it is cost effective and can be prepared in-house based on the functionality required. Hence, the present review focuses on the properties of the co-processed directly compressible adjuvants available in the market.

Compressive Strength↗

PubMed2003

Processing of nimesulide-PEG 400-PG-PVP solid dispersions: preparation, characterization, and in vitro dissolution.

The objective of this investigation was to study the influence of dissolution enhancers such as polyethylene glycol 400, propylene glycol, polyvinylpyrrolidone K30, sodium lauryl sulfate, and Tween 80 on in vitro dissolution of a model active pharmaceutical material--nimesulide. Preliminary studies were conducted using a physical blend of nimesulide, and the adjuvants and solid dispersions were prepared using solvent evaporation and cogrinding methods. Aqueous solution of adjuvants was first triturated with nimesulide, followed by mixing with lactose and microcrystalline cellulose, and finally water was evaporated under vacuum in a cogrinding method. A 33 factorial design was adopted in a cogrinding method using the concentration of polyethylene glycol 400, propylene glycol, and polyvinylpyrrolidone K30 as independent variables. Tween 80 and sodium lauryl sulfate were added in all the batches. Full and reduced models were evolved for different dependent variables. The reduced models were validated using two checkpoints. Angle of repose < 35 degrees, percentage of drug released in 30 min (Q30) > 40%, 45 min (Q45) > 50%, and 120 min (Q12) > 60% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependent variables. Polyvinylpyrrolidone was found to be more effective in increasing the drug dissolution, compared with polyethylene glycol 400 and propylene glycol. The granule flow was adversely affected when high levels of liquid adjuvants were used in formulations. Wettability study was conducted to measure wetting time for pure drug and the optimized batch. Improved drug dissolution was attributed to improved wetting and the solubilizing effect of adjuvants from the pseudosolid dispersions of nimesulide. Significant improvement in drug dissolution was observed (Q120 = 70%), compared with pure drug powder (Q120 = 15%). In conclusion, dissolution of nimesulide can be modulated using an appropriate blend of pharmaceutical adjuvants.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

Compressive Strength↗

PubMed2002

Novel use of similarity factors f2 and Sd for the development of diltiazem HCl modified-release tablets using a 3(2) factorial design.

The objective of this study was to develop modified-release tablets of diltiazem HCl using a direct compression technique. A 3(2) factorial design was employed using the amount of alkali-treated guar gum and cetyl alcohol as independent variables. This article proposes the use of a novel approach-f2 and Sd values as dependent variables-to evaluate the effect of selected independent variables along with other dependent variables (i.e., percentage drug released in x min, Yx; time required for z% drug release, tz; and mean dissolution time (MDT)). It is concluded that when a decision is to be made for the selection of a best batch, it is perhaps more realistic to use the f2 or Sd value which takes into account the dissolution profile as a whole, as opposed to Yx and tz values which use just one point from the dissolution plot. The batch showing the f2 value nearest to 100 or the Sd value nearest to zero is ranked as the best batch (diltiazem HCl 90 mg, alkali-treated guar gum 80 mg and cetyl alcohol 15 mg). The gel strength and matrix erosion of the formulated tablets were dependent on the type and amount of the adjuvants. The drug release rate is well correlated with matrix erosion. The kinetics of drug release fitted best to the Korsmeyer and Peppas model. It is concluded that by using a proper combination of the hydrophilic polymer and cetyl alcohol one can achieve a desirable drug release pattern.

Delayed-Action Preparations↗

PubMed2000

Novel mathematical method for quantitative expression of deviation from the higuchi model.

A simple mathematical method to express the deviation in release profile of a test product following Higuchi's kinetics from an ideal Higuchi release profile was developed. The method is based on calculation of area under the curve (AUC) by using the trapezoidal rule. The precision of prediction depends on the number of data points. The method is exemplified for 2 dosage forms (tablets of diltiazem HCl and microspheres of diclofenac sodium) that are designed to release the drug over a 12-hour period. The method can be adopted for the formulations where drug release is incomplete (<100%) or complete (100%) at last sampling time. To describe the kinetics of drug release from the test formulation, zero-order, first-order, Higuchi's, Hixson-Crowell's, and Weibull's models were used. The criterion for selecting the most appropriate model was based on the goodness-of-fit test. The release kinetics of the tablets and microspheres were explained by the Higuchi model. The release profiles of the test batches were slightly below the ideal Higuchi release profile. For the test products, observed percentage deviation from an ideal Higuchi profile is less than 16% for tablets and less than 11% for microspheres. The proposed method can be extended to the modified release formulations that are designed to release a drug over 6, 18, or 24 hours. If the data points are not evenly separated, the ideal drug release profile and AUC are calculated according to the specific sampling time. The proposed method may be used for comparing formulated products during the research and development stage, for quality control of the products, or for promoting products by comparing performance of the test product with that of the innovator's product.

Chemistry, Pharmaceutical↗

PubMed2000

Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

Calcium Channel Blockers↗

PubMed1999

Formulation design and optimization of modified-release microspheres of diclofenac sodium.

The present study deals with the preparation of microspheres of diclofenac sodium using cross-linked poly(vinyl alcohol) (PVA). A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for developing the microspheres. The PVA to the drug ratio X1 and amount of glutaral-dehyde cross-linking agent X2 were chosen as the independent variables. The time required for 50% drug dissolution t50 in phosphate buffer (pH 7.2) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable t50. Based on the results of multiple linear regression analysis and F statistics, it may be concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. A response surface plot is presented to show the effects of X1 and X2 on t50. The drug release pattern fit the Higuchi model well. A model was validated for accurate prediction of the drug dissolution profile with constraints on the percentage drug release in the first, fifth, and seventh hours. The data of a selected batch were subjected to an optimization study, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Analysis of Variance↗

PubMed1998

Formulation optimization of controlled release diclofenac sodium microspheres using factorial design.

Diclofenac sodium is an ideal candidate for incorporation in a controlled release device to diminish its adverse effects after oral administration. Microspheres were prepared by using sodium alginate as a polymer and CaCl2 as a cross-linking agent. In this investigation, 3(3) full factorial design was used to investigate the joint influence of the three variables: the stirring speed (X1), concentration of CaCl2 (X2) and % of heavy liquid paraffin in a blend of heavy and light liquid paraffin in the dispersion medium (X3) on the time of 80% drug dissolution (t80). Potential variables such as concentration of sodium alginate and drug: sodium alginate ratio were kept constant in the experimental design. A statistical model with significant interaction terms is derived to predict t80. The results of multiple linear regression analysis and F-statistics revealed that for obtaining controlled drug release, the microspheres should be prepared using relatively lower stirring speed, higher concentration of CaCl2 and higher percentage of heavy liquid paraffin in the dispersion medium. The X1X2 and X2X3 interactions were found to be statistically significant in nature. A response surface plot is presented to show the effects of X1, X2 and X3 on t80. The drug was released by diffusion of anomalous type. A model was validated for accurate prediction of drug release profile. Acceptable batches were identified in the experimental design with constraints on percentage drug released in 1, 6 and 8 h.

Alginates↗

PubMed1998

Preliminary investigations in matrix-based tablet formulations of diltiazem hydrochloride containing succinic acid-treated methylcellulose.

The feasibility of using succinic acid-treated methylcellulose in matrix-based tablets of diltiazem hydrochloride was investigated in this study. A 2(3) factorial design was employed to investigate the effect of ratio of methylcellulose to succinic acid, amount of ethyl alcohol, and drying time on the percentage drug dissolved in 300 min. The tablets were prepared by wet granulation technique. The ratio of methylcellulose to succinic acid was found to significantly influence the swelling and gelling characteristics of the polymer. Carbonyl peak was found in the infrared (IR) spectra of the samples modified using succinic acid, suggesting the presence of an ester group. The results of an ANOVA test revealed that the significance of the ratio of methylcellulose to succinic acid and drying time was greater in magnitude than that of amount of alcohol in controlling the drug release in 300 min. The results of F-test revealed that the zero-order model fits well to the in vitro dissolution data. The characteristics of methylcellulose can be changed by reacting it with succinic acid and the resultant product can be used as a hydrophilic matrixing agent.

Calcium Channel Blockers↗

PubMedDate not supplied

Studies in release behavior of diltiazem HCl from matrix tablets containing (hydroxypropyl)methyl cellulose and xanthan gum.

(Hydroxypropyl)methyl cellulose and xanthan gum were used as hydrophilic matrixing agents for preparing modified release tablets of diltiazem HCl. The amount of (Hydroxypropyl)methyl cellulose and xanthan gum exhibited significant effect on drug release from the tablets prepared by direct compression technique. Xanthan gum showed a higher ability to retard the drug release than (Hydroxypropyl)methyl cellulose. A 2(2) + 1 factorial design was adopted to study the effect of amount of (Hydroxypropyl)methyl cellulose and xanthan gum on percent drug released in first hour (Y60) and the time required for 90% drug dissolution (t90). A response surface plot is generated for investigating the effect of the independent variables on t90. The tablets containing 90 mg diltiazem HCl, 45 mg (Hydroxypropyl)methyl cellulose and 45 mg xanthan gum showed drug release upto 12 h. The value of similarity factor, f2, for the selected batch was found to be 85.1 when the dissolution study was carried out in water or simulated gastric fluid, indicating pH independent drug dissolution. The selected batch also showed a comparable release profile with a market product (f2 = 60.2). Linear relationship was observed between percent drug released and degree of swelling. The kinetics of the drug release fitted well to the Hixson-Crowell equation. It can be concluded that by using a suitable blend of (Hydroxypropyl)methyl cellulose and xanthan gum desired modified drug release can be achieved.

Antihypertensive Agents↗