Tablet Excipients Research Articles

Evaluation of Two Olibanum Resins as Rate Controlling Matrix Forming Excipients in Oral Sustained Release Tablets

Olibanum is an oleo-gum resin which is economically and culturally valuable product obtained from several species of the genus Boswellia. In this study, the resins extracted from local olibanum: Boswellia papyrifera (Tigray type) and Boswellia rivae (Ogaden type) were evaluated as matrix forming agents in sustained release tablet formulations employing diclofenac sodium as a model drug. Some physico-chemical characterization of the resins revealed low solubility, moisture content and swelling ratio. Sustained release matrix tablets containing 100 mg of diclofenac sodium were then prepared using different proportions of the olibanum resins by wet granulation and direct compression methods, and evaluated for their pharmacotechnical properties and in vitro drug release kinetics. Both resins produced matrix tablets with acceptable weight variation, hardness and friability. Dissolution studies showed that the olibanum resins sustain the drug release beyond 12 h. Drug release from the olibanum resins matrix tablets were best fitted to the Korsmeyer-Peppas model with the mechanism of drug release generally following non-Fickian diffusion process. Diclofenac release profiles from some of the formulated tablets were comparable to that of the commercial sustained release tablet Diclo-Denk® Retard.Keywords: Olibanum resin, matrix tablet, diclofenac sodium, sustained release, release kinetics

Evaluation of hydrophilic, hydrophobic and waxy matrix excipients for sustained release tablets of Venlafaxine hydrochloride

Objective: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets.Materials and methods: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism.Results: Dissolution data showed that commercial formulations Venlor XR® and Venfax PR® released the entire drug withIn 8 h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14–15 h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively.Conclusion: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations.

Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296nm and metoprolol succinate has absorbance maxima at 223nm in methanol. The linearity was obtained in the concentration range of 2-16μg/ml and 3-24μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. Result: The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate.

Validation of densitometric and videodensitometric TLC methods for analysis of vigabatrin in pharmaceutical formulations

Two new, simple, precise and accurate thin-layer chromatography methods with densitometric and videodensitometric detection were developed for the determination of vigabatrin in pharmaceutical preparations. The analysis was performed on silica gel 60 F254 plates in horizontal chambers with acetone-butan-2-one-formic acid-water (40:45:5:10, v/v), as mobile phase. The method is based on the reaction of the primary amino group of vigabatrin with ninhydrin reagent producing a colored product which absorbs maximally at 483 nm. Videodensitometric assay was performed at visible light. Calibration plots were constructed in the range 2.0 - 20.0 µg/spot with good correlation coefficients r=0.9991 and r=0.9949 for densitometry and videodensitometry, respectively. The LOD was 0.6 µg and 0.8 µg per spot for densitometric and videodensitometric assay, respectively; the LOQ was 1.5 µg per spot for both methods. The active substance was extracted from tablets with methanol. The mean ± SD recovery from commercially available tablets was 100.22 ± 0.61 % (n=6) for the both methods. Tablet excipients did not interfere with the chromatography. Finally, the methods were compared statistically in respect of precision and accuracy. No significant differences were observed.

Reflectance Near-Infrared Spectroscopic Method with Chemometric Techniques for Simultaneous Determination of Chondroitin, Glucosamine, and Methyl Sulfonyl Methane

Reflectance near-IR (RNIR) spectroscopy was used for the simultaneous determination of chondroitin (CH), glucosamine (GO), and methyl sulfonyl methane (MSM) in tablets. Simple sample preparation was done by grinding, sieving, and compression of the tablets for improving RNIR spectra. Principal component regression and partial least squares (PLS-1 and PLS-2) were successfully applied to quantify the three components in the studied mixture using information included in RNIR spectra in the range of 4350-9100 cm(-1). The calibration model was developed with drug concentration ranges of 14.5-44.2% (w/w) for CH, 18.4-55.3% (w/w) for GO, and 6-18.6% (w/w) for MSM with addition of tablet excipients to the calibration set in the same ratio as in the tested tablets. The calibration models were evaluated by internal validation, cross-validation, and external validation using synthetic and pharmaceutical preparations. The proposed method was applied for analysis of six batches of the pharmaceutical product. The results of the proposed method were compared with the results of the pharmacopoeial method for the same batch of the pharmaceutical product. No significant differences between the results were found. The RNIR method is accurate and precise, and can be used for QC of pharmaceutical products.

Pharmaceutical design of a new lactose-free coprocessed excipient: application of hydrochlorothiazide as a low solubility drug model

Most co-processed excipients used in direct-compression tablets contain lactose, which prevents lactose-intolerant patients from taking such tablets. Therefore, a novel lactose-free co-processed excipient for direct compression tablets has been prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used as primary excipients which underwent a wet granulation process and factorial experiment in order to ascertain the best prototype. Finally, the best two prototypes were added to hydrochlorothiazide, which has chosen as the model drug because of its low solubility. An extensive characterization of the new excipient as well as the drug loaded tablets is reported. Our results show adequate parameters (rheological and compression behavior, uniformity of weight, disintegration, friability, crushing force and cohesion index). Moreover, the biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic function and fast drug release.

SIMULTANEOUS ESTIMATION OF CEFIXIME AND CLOXACILLIN IN BULK AND TABLET FORMULATION BY RP-HPLC METHOD

A simple, economic, selective, precise and accurate high-performance liquid chromatographic (RP-HPLC) method for the analysis of cefixime and cloxacillin in both bulk drug and pharmaceutical formulations was developed and validated in the present study. This method has shown good resolution for cefixime, cloxacillin and formulation excipients of tablets. The mobile phase consisted of phosphate buffer (25 mM):methanol: acetonitrile (40: 45: 15 v/v/v), pH 4.6 adjusted with orthophosphoric acid. HPLC analysis of cefixime and cloxacillin was carried out at a wavelength of 225 nm with flow rate of 1.0 mL min-1. The method was quantitatively evaluated in terms of linearity, precision, accuracy (recovery), selectivity and robustness. The method is simple, convenient and suitable for the analysis of cefixime and cloxacillin in bulk and its formulation.

Development and evaluation of a novel pellet-based tablet system for potential colon delivery of budesonide.

Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3 : 7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24 h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets.

SIMULTANEOUS SPECTROPHOTOMETRIC ESTIMATION OF THIOCOLCHICOSIDE AND DEXKETOPROFEN TROMETAMOL IN PHARMACEUTICAL DOSAGE FORM

The present manuscript describes simple, sensitive, rapid, accurate, precise and economic dual wavelength spectrophotometric method for simultaneous determination of Thiocolchicoside and Dexketoprofen trometemol in combined tablet dosage form. The utility of dual wavelength data processing program is its ability to calculate unknown concentration of components of interest in a mixture containing an interfering component. The method was based on property of additivity of absorbances. The two wavelengths on UV spectrum of Thiocolchicoside were found out where it showed same absorbance, which were 368 nm and 284.60 nm. At 368 nm Thiocolchicoside showed some absorbance whereas Dexketoprofen trometemol showed zero absorbance. Both the drugs gave absorbance at 284.60 nm. The method involved solving of an equation based on measurement of absorbances at two wavelengths 284.6 and 368 nm. The two drugs follow Beer-Lambert’s law over the concentration range of 2-24 µg/ml. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The results of analysis have been validated statistically and by recovery studies.

The use of single particle mechanical properties for predicting the compressibility of pharmaceutical materials

The study's primary goal was to examine the possible use of single particle mechanical properties to estimate the compressibility behaviour of a tablet's excipients during compaction. Nanoindentation was utilised to measure individual mechanical properties (Young's modulus, nanoindentation hardness, energy of elastic and plastic deformation). On the bulk scale, studied excipients' compressibility was determined by Heckel and Walker models. Single particle hardness was found to provide direct information regarding an excipient's plasticity since an excellent correlation was established with the Walker model on the bulk level. A moderate correlation was obtained with the Heckel model due to its lack of fit for brittle materials. The indentation energy on a single level effectively differentiates materials in which plastic deformation dominates from those materials in which brittle fractures prevail. Elastic properties of materials can be successfully predicted by measuring the energy of elastic deformation on a single scale since an excellent correlation was observed with the bulk parameters such as energy of elastic deformation and the tablets' elastic relaxation index.We found that individual mechanical properties of a tablet's excipients greatly control the materials' deformation behaviour during tablet production despite of numerous other processes occurring during compression in the tablet die such as friction, bonding and local mechanical stress.

Effects of highly hygroscopic excipients on the hydrolysis of simvastatin in tablet at high relative humidity

Effects of highly hygroscopic sorbitol, citric acid, sodium carboxymethyl cellulose or polyvinylpolypyrrolidone, on the hydrolysis of simvastatin in tablets at 25°/90% RH were studied. The simvastatin tablets were prepared by direct powder compression. Simvastatin and its hydrolyte, simvastatin acid, were quantitatively analysed by high performance liquid chromotography. The hygroscopicity, water swelling ratio, water solubility and pH of the four hygroscopic excipients were investigated. During the investigation period, the weight gain of sorbitol or citric acid increased faster than that of polyvinylpolypyrrolidone or sodium carboxymethyl cellulose at 25°/90% RH, accordingly, the moisture sorption of the tablets containing citric acid or sorbitol (T-3 or T-6) were more than that of the tablets containing sodium carboxymethyl cellulose or polyvinylpolypyrrolidone (T-4 or T-5). The increase of simvastatin acid content with time at 25°/90% RH for the tablets was in the following order: T-6 < T-4 < T-3 < T-5. The effects of the four excipients on the hydrolysis of simvastatin in tablet were related to not only their hygroscopicity but also their other properties, such as moisture retention capacity and pH. Sorbitol as hygroscopic excipient in tablet can most effectively prevent the hydrolysis of simvastatin in tablet.

Determination of human growth hormone in pure and pharmaceutical dosage form by spectrofluorometry and high performance liquid chromatography

In this study, a new and rapid spectrofluorometry and high performance liquid chromatography (HPLC) methods were developed for determination of human growth hormone in pure and pharmaceutical dosage form. The solvent system, wavelength of detection and chromatographic conditions were optimized in order to maximize the sensitivity of both the proposed methods. The linearity was established over the concentration range of 1.25-50?g mL-1 for spectrofluorometry and 10-75?g mL-1 for HPLC method. The intra- and inter-day relative standard deviation (RSD) was less than 8.46 and 5.98% for spectrofluorometry and HPLC, respectively. Limits of quantitation were determined as 0.075 and 7.5?g mL-1 for spectrofluorometry and HPLC, respectively. No interference was found from tablet excipients at the selected assay conditions. The methods were applied for the quality control of commercial growth hormone dosage form to quantify the drug and to check the formulation content uniformity.

Stability Indicating Rp-Hplc Method for the Estimation of Montelukast in Pharmaceutical Dosage Form

A simple, specific, accurate, precise and stability-indicating reverse phase high performance liquid chromatography (RP-HPLC) method is developed for estimation of montelukast in tablet dosage form. The HPLC method, C-8 Column consisting of (25mm x 4.6mm x 5um - BDS) i.d in isocratic mode, with mobile phase containing 0.01M Potassium di-hydrogen orthophosphate buffer and acetonitrile in the ratio of 35:65 v/v was used. The flow rate was 1mL min -1 and effluent was monitored at 222 nm. Retention time was found to be 3.08min, respectively. The method was validated in terms of Linearity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ) etc. in accordance with ICH guidelines. Linear regression analysis data for the calibration plot showed that there was good linear relationship between response and concentration in the range of 10 - 100 µg/ml respectively. The LOD and LOQ values for HPLC method were found to be 0.03 and 0.09 µg/ml respectively. No chromatographic interference from tablet excipients was found. The proposed method was successfully used for estimation of montelukast in tablet dosage form.

Formulation and characterization of ketoprofen liquisolid compacts by Box-Behnken design

Introduction:Liquisolid technique is used in delivery of lipophilic and poorly water soluble drugs through oral route. It involves dissolving water insoluble drugs in nonvolatile solvents and converting into acceptably flowing and compressible powders. The objective of the present work was to enhance the dissolution rate of ketoprofen using microcrystalline cellulose as carrier, aerosil 200 as coating material, and polyethylene glycol as nonvolatile water miscible liquid vehicle.Materials and Methods:The drug concentration was kept constant in all formulations at 40% w/w. Optimization was carried out using Box–Behnken design by selecting liquid load factor, amount of coating material, and amount of magnesium oxide as independent variables; cumulative percentage drug release and angle of repose were considered as dependent variables.Results:The Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) studies revealed that there was no possible interaction between drug and tablet excipients. Prepared ketoprofen liquisolid tablets were evaluated for hardness, weight variation, friability, in-vitro disintegration time, drug content uniformity, and in-vitro dissolution studies. The optimized formulation yielded the response values, which were very close to the predicted values. The accelerated stability studies conducted showed that liquisolid tablets were not affected by ageing and there were no appreciable changes in the drug content.

Comparative Evaluation of Zea mays (L.) and Ipomoea batatas (L.) as a Pharmaceutical Excipient

This investigation aims at comparing starches from two grains: Maize (Zea mays) and Sweet potato (Ipomoea batatas) grains. These grains are used mainly as foods and they contain high amount of carbohydrate. The presence of starch in these grains varies and thus their use as pharmaceutical excipients will vary to the degree of their starch functionality. The powders obtained were characterized for their particle size, particle size distribution. The organoleptic and physicochemical characterization such as viscosity, hydration capacity, swelling capacity, moisture sorption capacity, pH, flow rate and porosity, Carr's index and Hausner's ratio were evaluated. Maize starch showed the least Carr's index, Hausner ratio, porosity, moisture sorption capacity and the greatest flow rate. Sweet potato starch showed the highest hydration capacity and swelling capacity. The results obtained showed that between the two starches in relation to their flowability, maize starch possesses the best flow property. Compatibility of Etoricoxib with maize and sweet potato starch was evaluated by IR spectra and found that both Etoricoxib is compatible along with maize and sweet potato starch. This knowledge of starch properties will help to explain the behavior of these starches when used as tablet excipients.

Genetic Algorithms-Based Approach for Wavelength Selection in Spectrophotometric Determination of Vitamin B12 in Pharmaceutical Tablets by Partial Least-Squares

This study illustrated the genetic algorithms (GA) is useful tool in wavelength selection for the spectrophotometric determination of vitamin B12 in pharmaceutical tablets by partial least-squares calibration procedure (PLS). Because of interference in the spectra, a training set of the mixtures of vitamin B12 and tablet excipients was built to be used as calibration set for modeling. The absorption spectra of all solutions were recorded each 1nm in the range 354-600nm, using 0.1N hydrochloric acid as solvent. A validation set was employed to verify the models and a commercial sample was analysed. GA-PLS model leads to 86% improvement of predictive ability for vitamin B12, when comparing with full spectrum PLS model. It is concluded that only some variables in GA-PLS modeling are relevant for prediction and removing the non-relevant variables can improve the predictive capability.

Simultaneous Estimation of Nebivolol Hydrochloride and Hydrochlorothiazide in Tablets by TLC-Densitometry

A simple, rapid and accurate thin-layer chromatography (TLC)–densitometric method has been established and validated for the simultaneous determination of nebivolol hydrochloride and hydrochlorothiazide in tablets. The method is based on TLC separation of the two drugs followed by densitometric measurements of their spots at 281 nm. The separation was carried out on Merck TLC aluminium plate of silica gel 60F 254 using toluene:ethyl acetate:methanol:ammonia (3:2.7:1.7:0.1 v/v/v) as a mobile phase. Nebivolol hydrochloride and hydrochlorothiazide gave sharp and well defined peak at Rf 0.68 and 0.38, respectively. Calibration curves for nebivolol hydrochloride and hydrochlorothiazide were linear in range 500-3000 ng/spot and 1000-6000 ng/spot, respectively. Method was successively applied to tablet formulation. No chromatographic interferences from the tablet excipients were found. The method was validated in accordance with the requirements of ICH guidelines.

Development and Validation of a Spectrophotometric Method for Quantification and Dissolution Studies of Glimepiride in Tablets

The objective of present study was to develop and validate an analytical method for quantitative determination and dissolution studies of glimepiride in tablets. The glimepiride shows absorption maxima at 225 nm and obeyed Beer's law in the range of 6.0 – 14.0 µg/mL. The limit of detection and limit of quantitation were 0.06, and 0.17 µg/mL respectively. Percentage recovery of glimepiride for the proposed method ranged from 99.32 to 100.98% indicating no interference of the tablet excipients. It was concluded that the proposed method is simple, easy to apply, economical and used as an alternative to the existing spectrophotometric and non-spectrophotometric methods for the routine analysis of glimepiride in pharmaceutical formulations andin vitrodissolution studies.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: Drug release and fronts movement kinetics

A previous paper [1] deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.

Development and Validation of New Assay Method for the Simultaneous Analysis of Diltiazem, Metformin, Pioglitazone and Rosiglitazone by RP-HPLC and its Applications in Pharmaceuticals and Human Serum

Simple, sensitive, rapid, and accurate high-performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of diltiazem, metformin, pioglitazone, and rosiglitazone hydrochloride in raw materials, their pharmaceutical formulations, and human serum. In HPLC, all the above drugs were chromatographed using acetonitrile-methanol-water (30:20:50, v/v, pH 2.59 ± 0.02) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The separation is carried out on a Hiber, 250-4.6 RP-18 column, equipped with a UV-vis detector at 230 nm. All the antidiabetic drugs eluted at different retention time and each showed a good resolution from diltiazem. The method is successfully applied to pharmaceutical formulations because no chromatographic interferences from the tablet excipients are found. The method is found to be linear, accurate, and precise with apposite detection and quantification limit. Suitability of the method for the quantitative determination of the drugs is proven by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines. The validation results, together with statistical treatment of the data, demonstrated the reliability of this method.