Evaluation of Mujol as a Direct Compression Excipient in Oxytetracycline Hydrochloride Tablet Formulations

Abstract

The physical properties of oxytetracyc1ine hydrochloride tablets compressed with Musol, a new autocompressib1e vehicle obtained by chemical modification of an edible seed polysaccharide were studied, Avice1 PH 101, Fast-f1o lactose and Emcompress were used as basis for comparison.

With the exception of those tablets containing Emcompress, good disintegration and dissolution profiles were obtained in all the batches formulated. The dissolution characteristics of the tablets did not change significantly after storage in the dark at 30°C for 96 weeks.     

An Evaluation of Hydroxypropyl Starch as Disintegrant and Binder in Tablet Formulation

Hydroxypropyl and pregelatinized hydroxypropyl starch were evaluated as disintegrant and binder in tablet formulations. The study showed that the use of pure hydroxypropyl starch showed no advantage as a disintegrant or binder over the actually available tablet ingredients. Pregelatinized hydroxypropyl starch showed some good disintegrating properties and could be used as a binder in wet granulation.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression, Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression,Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Optimization of Tablet Formulations Containing

Abstract

An optimized direct compression tablet formulation of a conventional theophylline tablet was developed using the technique of response surface methodology and successive quadratic programming (SQP). The response surfaces were obtained from fitting data generated from a secondorder uniformprecision rotatable hexagonal experimental design. The tablet formulation was optimized for mean in vitro dissolution time using disintegration time, ejection force, friability and hardness, as constraints within the experimental region by the SQP technique. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis for the optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values.     

Optimization of Tablet Formulations Containing

An optimized direct compression tablet formulation of a conventional theophylline tablet was developed using the technique of response surface methodology and successive quadratic programming (SQP). The response surfaces were obtained from fitting data generated from a secondorder uniformprecision rotatable hexagonal experimental design. The tablet formulation was optimized for mean in vitro dissolution time using disintegration time, ejection force, friability and hardness, as constraints within the experimental region by the SQP technique. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis for the optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values.     

Bioequivalence Evaluation of Two Formulations of Doxazosin Tablet in Healthy Thai Male Volunteers

ABSTRACT

The bioequivalence of two doxazosin 2 mg tablets was determined in 24 healthy Thai male volunteers after one single dose in a randomized cross-over study with a one week washout period. The study was conducted at Faculty of Pharmaceutical Sciences and Health Sciences Research Institute, Naresuan University, Phitsanulok, Thailand. Reference (Cardura®, Heinrich Mack Nachf. GmbH & Co. GK, Illertissen, Germany) and test (Dozozin-2®, Umeda Co., Ltd., Bangkok Thailand) were administered to volunteers after overnight fasting. Blood samples were collected at specified time intervals and plasma was separated. The validated HPLC method with fluorescence detection was used for quantification of doxazosin in plasma samples. The pharmacokinetic parameters, T_max, C_max, AUC_t, AUC_∞, T_1/2, λ_z, Cl and V_d, were determined from plasma concentration time profile of both formulations by using non-compartment analysis. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands. The analysis of variance (ANOVA) using log-transformed C_max, AUC_t, and AUC_∞ did not show any significant difference between two formulations. The point estimates and 90% confidence intervals for C_max, AUC_t and AUC_∞ were within the acceptance range (0.80–1.25), satisfying the bioequivalence criteria of the Thailand Food and Drug Administration Guidelines. These results indicate that Dozozin-2® is bioequivalent to Cardura® and, thus, may be prescribed interchangeably.     

Evaluation of Formal in-Case in as a Tablet Disintegrant

Formalin-casein has been proposed as a tablet disintegrant under the trade name o f Esma-sprenq. The significance of water penetration on the disintegration mechanism has been evaluated by using different tablet constituents and by modifyinq the hydrophobicity inside the tablet. Formalin-casein appears to be a powerful disintegration agent when a sufficiently hydrophobicity network has been created within the tablet. Swelling of the disintegrant has also been considered and evaluated under different conditions. However, this mechanisrn appears to be negligible in the disintegration process. In addition, a number of compressional characteristics were studied.     

Granulation Surface Area as Basis for Magnesium Stearate Concentration in Tablet Formulations

Abstract

Tablets provide drug delivery in a convenient and uncomplicated manner. Despite this apparent simplicity, they must comply with a formidable number of physico-chemical compendial requirements defined by specifications and test methods. What these specifications indirectly control is that each dosage form or each lot of dosage form my vary but the variance is held within stated limits.

This communication focuses on the weight variation of formulation ingredients that my be allowed in general and for magnesium stearate in particular and to define a relationship between the lubricant level and granulation surface area of a calcium phosphate matrix to obtain optimal tablet properties.     

Granulation Surface Area as Basis for Magnesium Stearate Concentration in Tablet Formulations

Tablets provide drug delivery in a convenient and uncomplicated manner. Despite this apparent simplicity, they must comply with a formidable number of physico-chemical compendial requirements defined by specifications and test methods. What these specifications indirectly control is that each dosage form or each lot of dosage form my vary but the variance is held within stated limits.

This communication focuses on the weight variation of formulation ingredients that my be allowed in general and for magnesium stearate in particular and to define a relationship between the lubricant level and granulation surface area of a calcium phosphate matrix to obtain optimal tablet properties.     

Use of a Desk-Top Computer in a Search-Type Optimization of Tablet Formulations

The use of a desk-top computer in the field of formulation and process optimization is described. To illustrate an application of this technique, a series of tablets has been prepared according to a classical optimization design to determine the optman levels of process variables which meet pre-established specifications for product variables (hardness, thickness, etc.) based on second order polynomial predictor equations for each measured parameter.     

Use of a Desk-Top Computer in a Search-Type Optimization of Tablet Formulations

Abstract

The use of a desk-top computer in the field of formulation and process optimization is described. To illustrate an application of this technique, a series of tablets has been prepared according to a classical optimization design to determine the optman levels of process variables which meet pre-established specifications for product variables (hardness, thickness, etc.) based on second order polynomial predictor equations for each measured parameter.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Abstract

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

The Evaluation of Fine-Particle Hydroxypropylcellulose as a Roller Compaction Binder in Pharmaceutical Applications

In solid dosage manufacturing, roller compaction technology plays an important role in providing cost control and a quality product. The objective of this study was to evaluate the effectiveness of fine-particle hydroxypropylcellulose (HPC) as a dry binder in roller compaction processing. The formula included acetaminophen (APAP), microcrystalline cellulose, fine-particle HPC, croscarmellose sodium, and magnesium stearate. The fine-particle HPC was incorporated into the formula at 4%, 6%, and 8% w/w levels. Three compaction pressures (30, 40, and 50 bars) were used for each formulation. The roller compaction equipment used in this study had a processing capacity of 40 to 80 kg/hr. A tablet compression profile was generated on a rotary tablet press, and compression forces used were 5, 10, 15, 20, and 25 kN. The significant criteria for tablet evaluation were capping, hardness, friability, ejection force, and drug dissolution. As the binder concentration of HPC increased, tablet capping decreased, and tablet friability improved. As the concentration of HPC increased, only slight differences were noted in tablet hardness. All the formulations pass the USP requirement of 80% APAP dissolved within 30 min. Using 8% HPC could eliminate the formula capping problem. The friability results were less than 1% at all compression forces. The minimum tablet ejection forces were found in the formulations prepared under 40 bars compaction pressure. The utility of fine-particle HPC as a roller compaction binder was established. The applicable binder concentrations and roller compaction pressures were found. Using HPC at these binder levels and operating parameters could overcome capping and friability problems and achieve the optimal tablet dosage forms.     

An Evaluation of Croscarmellose as a Tablet Disintegrant in Direct Compression Systems

Abstract

The disintegrant actions of croscarmellose type A (Ac-Di-Sol, FMC Corp.) and croscarmellose type B (CLD-2, Buckeye Cellulose Corp.) have been compared to that of corn starch in direct compression tablets in which microcrystalline cellulose (Avicel PH101, FMC Corp.) was the matrix. Two types of formulations were examined using either pyridoxine or hydrochlorothiazide as drug. The data clearly shows that both forns of croscarmellose are markedly superior to corn starch and are active at quite low concentrations. The CLD-2 may promote more rapid dissolution in some systems than Ac-Di-Sol.     

An Evaluation of Croscarmellose as a Tablet Disintegrant in Direct Compression Systems

The disintegrant actions of croscarmellose type A (Ac-Di-Sol, FMC Corp.) and croscarmellose type B (CLD-2, Buckeye Cellulose Corp.) have been compared to that of corn starch in direct compression tablets in which microcrystalline cellulose (Avicel PH101, FMC Corp.) was the matrix. Two types of formulations were examined using either pyridoxine or hydrochlorothiazide as drug. The data clearly shows that both forns of croscarmellose are markedly superior to corn starch and are active at quite low concentrations. The CLD-2 may promote more rapid dissolution in some systems than Ac-Di-Sol.     

An Evaluation of Smecta as a Tablet Disintegrant and Dissolution Aid

Abstract

Smecta is a nonfibrous Attapulgite (NFA), mostly composed of smectite. It was evaluated as a disintegrant in tablets made by direct compression as well as by wet granulation and using lactose and dicalcium phosphate as water soluble and water insoluble fillers, respectively. An inorganic clay, magnesium aluminum silicate (Veegum), a modified starch (Starch 1500), a cross-linked carboxymethyl cellulose (Ac-Di-Sol), and a cross-linked polyvinylpyrrolidone (Polyplasdone XL) were used for comparative evaluation. Smecta performed well as a disintegrant in tablets made by either method. It was superior to Veegum and Starch 1500, but inferior to Ac-Di-Sol and Polyplasdone XL. In tablets with Smecta, dissolution of hydrochlorothiazide (HCTZ) was superior to those with Ac-Di-Sol.     

An Evaluation of Smecta as a Tablet Disintegrant and Dissolution Aid

Smecta is a nonfibrous Attapulgite (NFA), mostly composed of smectite. It was evaluated as a disintegrant in tablets made by direct compression as well as by wet granulation and using lactose and dicalcium phosphate as water soluble and water insoluble fillers, respectively. An inorganic clay, magnesium aluminum silicate (Veegum), a modified starch (Starch 1500), a cross-linked carboxymethyl cellulose (Ac-Di-Sol), and a cross-linked polyvinylpyrrolidone (Polyplasdone XL) were used for comparative evaluation. Smecta performed well as a disintegrant in tablets made by either method. It was superior to Veegum and Starch 1500, but inferior to Ac-Di-Sol and Polyplasdone XL. In tablets with Smecta, dissolution of hydrochlorothiazide (HCTZ) was superior to those with Ac-Di-Sol.     

Studies on Controlled-Release Formulations of Diclofenac Sodium

The effects of various polymers on the release of diclofenac sodium from their matrices have been evaluated. In vitro release profiles of diclofenac sodium from ethylcellulose and hydroxypropylmethylcellulose (HPMC) K4M matrices showed that decreasing the concentration of ethylcellulose and increasing the concentration of HPMC K4M resulted in an increase in the release rate of diclofenac sodium. An increase in the amount of lactose in matrix resulted in an increase in the release rate of diclofenac sodium. It is suggested that the use of ethylcellulose or Precirol containing relatively large percentage concentrations of lactose in matrices will not provide zero-order release of diclofenac sodium from matrices. The best-fit release kinetics with the highest correlation coefficients was achieved with the Higuchi's plot followed by the zero-order. A straight line relationship was established bemeen the T_50% and the ratio of HPMC K4M to diclofenac sodium.