Effect of Polysorbates on Atenolol Release from Film-Coated Tablets

The effects of different concentrations of various polysorbates on the release rate of atenolol from film-coated tablets were evaluated. The release profile of atenolol showed that increasing the concentration of polysorbate resulted in an increase in the release rate of atenolol. The type of polysorbate had less effect on the release rate of atenolol. This study revealed that the release kinetic of atenolol from these film-coated tablets was a function of polysorbate concentration. Correlation coefficients of kinetic models could not solely determine the suitability of the models; the sum of the least square of differences also should be calculated when different kinetic models have similar correlation coefficients.     

Compaction of and drug release from coated pellets of different mechanical properties

The aim of this work was to relate the mechanical properties of film-coated pellets to their damage received during compaction, and to establish the significance of this damage for the release of a model drug from the resulting tablets. The formulations contained paracetamol and various excipient combinations chosen to provide different mechanical properties of the pellets, which were film-coated with Surelease® at various film thicknesses, and then compacted into tablets using three different compaction pressures. The drug release from the tablets was determined and compared to that of the uncompacted pellets. The compressibility and compactability of the various types of pellets was significantly influenced by the nature of the excipient combinations and binder liquids used to prepare the pellet cores, which also affected the drug release from the tablets. This could be attributed to the different responses of the pellets to compressive and shear stress. The film thickness and the mechanical properties of the film coating were found to be less important for tablet formation, but the film thickness played an important role in controlling the drug release rate from the tablets.     

A long acting ophthalmic gel formulations of atenolol

The main aim of pharmacotherapeutics, is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. In this study a trial was made to formulate atenolol, which is a beta-adrenergic blocker in a topical ophthalmic gel. Two polymers were used in this study, carboxymethylcellulose and sodium alginate in different concentrations. Atenolol was used in concentrations 0.5, 1, and 1.5% w/v. The in vitro release study was carried out. The results showed that the release rate of atenolol from gel preparations decreased as an inverse function of polymer concentration, while the release rate of the drug increased as the initial concentration increased. The data of drug release from the two polymers in different concentrations was plotted against the square root of time, and the diffusion coefficients (D), were calculated from the slope of the equation.

Intra-ocular pressure (IOP) measurements of the rabbit's eye treated with 1% w/v atenolol solution, and 1% w/v atenolol in two gel formulations with different concentrations of the polymer were determined. The two gel formulations showed that these polymers extended the duration of pressure reducing effect to 8 hr, when compared with atenolol solution. Area above the curve (AAC), maximum response, maximum time of response (t_max), and the duration of action were calculated.

The overall results of this study indicated that the gel formulations of atenolol could be used for the development of a long-acting ophthalmic formulation.     

A Long Acting Ophthalmic Gel Formulations of Atenolol

The main aim of pharmacotherapeutics, is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. In this study a trial was made to formulate atenolol, which is a beta-adrenergic blocker in a topical ophthalmic gel. Two polymers were used in this study, carboxymethylcellulose and sodium alginate in different concentrations. Atenolol was used in concentrations 0.5, 1, and 1.5% w/v. The in vitro release study was carried out. The results showed that the release rate of atenolol from gel preparations decreased as an inverse function of polymer concentration, while the release rate of the drug increased as the initial concentration increased. The data of drug release from the two polymers in different concentrations was plotted against the square root of time, and the diffusion coefficients (D), were calculated from the slope of the equation.

Intra-ocular pressure (IOP) measurements of the rabbit's eye treated with 1% w/v atenolol solution, and 1% w/v atenolol in two gel formulations with different concentrations of the polymer were determined. The two gel formulations showed that these polymers extended the duration of pressure reducing effect to 8 hr, when compared with atenolol solution. Area above the curve (AAC), maximum response, maximum time of response (t_max), and the duration of action were calculated.

The overall results of this study indicated that the gel formulations of atenolol could be used for the development of a long-acting ophthalmic formulation.     

Prediction of in vivo drug performance using in vitro dissolution coupled with STELLA: a study with selected drug products

Prediction of the in vivo performance of the drug product from the in vitro studies is the major challenging job for the pharmaceutical industries. From the current regulatory perspective, biorelevant dissolution media should now be considered as quality control media in order to avoid the risk associated. Physiological based pharmacokinetic models (PBPK) coupled with biorelevant dissolution medium is widely used in simulation and prediction of the plasma drug concentration and in vivo drug performance. The present investigation deals with the evaluation of biorelevant dissolution media as well as in vivo drug performance by PBPK modelling using STELLA® simulation software. The PBPK model was developed using STELLA® using dissolution kinetics, solubility, standard gastrointestinal parameters and post-absorptive disposition parameters. The drug product selected for the present study includes Linezolid film-coated immediate-release tablets (Zyvox), Tacrolimus prolonged-release capsules (Advagraf), Valganciclovir tablets (Valcyte) and Mesalamine controlled-release capsules (Pentasa) each belonging to different biopharmaceutics classification system (BCS). The simulated plasma drug concentration was analyzed and pharmacokinetic parameters were calculated and compared with the reported values. The result from the present investigation indicates that STELLA® when coupled with biorelevant dissolution media can predict the in vivo performance of the drug product with prediction error less than 20% irrespective of the dosage form (immediate release versus modified release) and BCS Classification. Thus, STELLA® can be used for in vivo drug prediction which will be helpful in generic drug development.     

Release Kinetics and Availability of Mebeverine Hydrochloride from Polycarbophil Loaded by Swelling

The release rate and mechanism of release of mebeverine hydrochloride were studied for commercial “Duspatalin” tablets and for different tablet formulations (F₁, F₂ & F₃) containing 20, 40 and 65% polycarbophil, respectively. The formulated granules were obtained by freeze drying of polycarbophil granules loaded with aqueous solution of the drug at 25°C by swelling of the polymer. The release of mebeverine hydrochloride from prepared tablet formulations was faster than that of Duspatalin tablets. The release rate of the drug increased as the polycarbophil content of the tablets increased. The calculated correlation coefficients for the release data fitted to various models showed that the release from Duspatalin tablets and F₂ follow first order kinetics, while release of F₁ approaches that of zero order. The release mechanism from F₃ could not be determined. DSC thermograms showed that there is an interaction between the drug and the polymer in aqueous medium, but not in the solid state.

The in-vivo guinea-pig studies revealed that mebeverine hydrochloride was released and absorbed from the tested formula (F₃), depressed the agonists-induced contractions 2 hrs after treatment but not after 4 hrs indicating rapid absorption and metabolism. The percentage inhibitions ranged from 40-85%. The treatment seems to antagonise barium chloride (BaCl₂)-induced contractions more than those induced by carbochol.     

Release Kinetics and Availability of Mebeverine Hydrochloride from Polycarbophil Loaded by Swelling

The release rate and mechanism of release of mebeverine hydrochloride were studied for commercial “Duspatalin” tablets and for different tablet formulations (F₁, F₂ & F₃) containing 20, 40 and 65% polycarbophil, respectively. The formulated granules were obtained by freeze drying of polycarbophil granules loaded with aqueous solution of the drug at 25°C by swelling of the polymer. The release of mebeverine hydrochloride from prepared tablet formulations was faster than that of Duspatalin tablets. The release rate of the drug increased as the polycarbophil content of the tablets increased. The calculated correlation coefficients for the release data fitted to various models showed that the release from Duspatalin tablets and F₂ follow first order kinetics, while release of F₁ approaches that of zero order. The release mechanism from F₃ could not be determined. DSC thermograms showed that there is an interaction between the drug and the polymer in aqueous medium, but not in the solid state.

The in-vivo guinea-pig studies revealed that mebeverine hydrochloride was released and absorbed from the tested formula (F₃), depressed the agonists-induced contractions 2 hrs after treatment but not after 4 hrs indicating rapid absorption and metabolism. The percentage inhibitions ranged from 40–85%. The treatment seems to antagonise barium chloride (BaCl₂)-induced contractions more than those induced by carbochol.     

Comparative Study of Aqueous and Organic Enteric Coatings of Chlorpheniramine Maleate Tablets

Two acrylic polymers (Eudragit® L 12.5 P and L 30 D) and a cellulosic polymer (cellulose acetate trimellitate, CAT) in organic and aqueous formulations were used in order to obtain an enteric coating on tablets containing clorpheniramine maleate as a water-soluble model drug. The coating of tablets was executed in a coating pan in similar conditions for each kind of solvent. The coated tablets were tested according to the delayed-release test of USP 23 (Method A). In our experimental conditions different amounts of polymers were needed to obtain an enteric coating. The lowest amount was in the case of Eudragit L 30 D (aqueous), after which appeared Eudragit L 12.5 P (organic), CAT (organic), and finally, CAT (aqueous) as the polymer that needed to be of the highest amount. During the dissolution test differences in the size and aspect of the tablets were observed according to the polymers. Acrylic polymers did not show changes in size and aspect, but CAT polymers showed a notable increase in size. me different behavior of the tablets during the dissolution test can explain the differences observed in the adjustment of the release data. The release data were tested assuming common kinetic models. In the present study it was observed that Eudragit L polymers release the drug in a first-order kinetic and that CAT releases it according to a zero-order kinetic.     

Communications Evaluation of Egg Albumin as a Filler for Prolonged Release Direct Compressed Tablets

Direct compressed tablets for drugs of different physico-chemical properties were prepared using egg albumin as tablet filler. The prepared tablets at different drug:egg albumin ratios as well as the powder blends used for the preparation of the tablets were evaluated. The drug dissolutions from the egg albumin tablets were slow and different release profiles were obtained depending on the type of the drug. The release kinetics from the albumin matrix were tested for different models and were found to be anomalous resembling release of drugs from swellable type of matrices. In order to elucidate the release mechanism, the interaction of drugs with egg albumin was examined by thermal analysis. In most cases release retardation was increased with the increase of egg albumin matrix density. In case of meclizine-HCl the release was not depending on the egg albumin matrix density and it was believed that the rate determining step for its release is drug solubility and/or dissociation of the drug-egg albumin complex.     

Comparative Study of Aqueous and Organic Enteric Coatings of Chlorpheniramine Maleate Tablets

Abstract

Two acrylic polymers (Eudragit® L 12.5 P and L 30 D) and a cellulosic polymer (cellulose acetate trimellitate, CAT) in organic and aqueous formulations were used in order to obtain an enteric coating on tablets containing clorpheniramine maleate as a water-soluble model drug. The coating of tablets was executed in a coating pan in similar conditions for each kind of solvent. The coated tablets were tested according to the delayed-release test of USP 23 (Method A). In our experimental conditions different amounts of polymers were needed to obtain an enteric coating. The lowest amount was in the case of Eudragit L 30 D (aqueous), after which appeared Eudragit L 12.5 P (organic), CAT (organic), and finally, CAT (aqueous) as the polymer that needed to be of the highest amount. During the dissolution test differences in the size and aspect of the tablets were observed according to the polymers. Acrylic polymers did not show changes in size and aspect, but CAT polymers showed a notable increase in size. me different behavior of the tablets during the dissolution test can explain the differences observed in the adjustment of the release data. The release data were tested assuming common kinetic models. In the present study it was observed that Eudragit L polymers release the drug in a first-order kinetic and that CAT releases it according to a zero-order kinetic.     

Evaluation of Eudragit RS-PO and Ethocel 100 matrices for the controlled release of lobenzarit disodium

Lobenzarit disodium is a drug for the treatment of rheumatoid arthritis. In this work, inert matrix tablets of lobenzarit disodium were prepared by direct compression using Ethocel® 100 and Eudragit® RS-PO as polymeric materials in different ratios. The obtained powder mixtures and tablets were evaluated from the rheological and technological points of view. The dissolution test was performed to evaluate the in vitro release kinetic of the matrices. The obtained dissolution profiles demonstrated that the matrices containing Eudragit RS-PO showed a slower release rate and therefore were more suitable for controlling the release of drug. The fit to the Higuchi model indicates that the drug release mechanism from these matrices was controlled by the diffusion step.     

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.     

Variation of composition of an enteric formulation based on Kollicoat MAE 30 D

Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.     

Kinetic and equilibrium studies in removing lead ions from aqueous solutions by natural sepiolite

The capacity of sepiolite for the removal of lead ions from aqueous solution was investigated under different experimental conditions. The Langmuir and Freundlich equations, which are in common use for describing sorption equilibrium for wastewater-treatment applications, were applied to data. The constants and correlation coefficients of these isotherm models for the present system at different conditions such as pH, temperature and particle size were calculated and compared. The equilibrium process was well described by the Langmuir isotherm model and the maximum sorption capacity was found to be 93.4 mg/g for the optimal experimental condition. The thermodynamic parameters (DeltaG(o), DeltaH(o) and DeltaS(o)) for lead sorption on the sepiolite were also determined from the temperature dependence. The influences of specific parameters such as the agitation speed, particle size and initial concentration for the kinetic studies were also examined. The sorption kinetics were tested for first order reversible, pseudo-first order and pseudo-second order reaction and the rate constants of kinetic models were calculated. The best correlation coefficients were obtained using the pseudo-second order kinetic model, indicating that lead uptake process followed the pseudo-second order rate expression.     

The influence of drug-excipient and drug-polymer interactions on butt adhesive strength of ranitidine hydrochloride film-coated tablets

The influence of fillers and polymeric films on adhesive strength of hydroxypropyl methylcellulose (HPMC) and Eudragit E100® films coated on ranitidine HCl tablets containing either spray-dried rice starch (SDRS) or lactose monohydrate as fillers after storage at 45°C/75% RH for four weeks was investigated by the use of butt adhesion technique. The adhesive strength of film-coated tablets of fillers without drug was found to slightly decrease after storage. In contrast, the adhesive strength of drug-containing film-coated tablets significantly reduced, the degree of which was higher for Eudragit E100® than HPMC. Physicochemical characterization by employing differential scanning calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) revealed that the drug was obviously incompatible with lactose and possibly mild interaction with Eudragit E100® was suggested. The results indicated that the adhesive strength of film-coated tablets would be affected not only by the drug-excipient interaction, but also by the drug-polymeric film interaction.     

Stability of Extemporaneous Norfloxacin Suspension

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different.     

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.     

Effect of Stearic Acid Particle Size on Surface Characteristics of Film-Coated Tablets

Raw material specifications are vital for many excipients used in the manufacture of tablets. Stearic acid powder is widely used in the pharmaceutical industry as a tablet lubricant. This study shows that the variation in particle size of stearic acid not only affects die wall lubrication properties (ejection force) but also affects surface characteristics of film-coated tablets. A coarser grade of stearic acid can dislodge from tablet surfaces during the film-coating process leaving pit marks, whereas a finer grade of stearic acid (less than 100 mesh) results in film-coated tablets having very smooth surfaces. The mechanism of pitting on the tablet surface is described. A specification for stearic acid particle size to overcome this problem is suggested.     

Stability of extemporaneous norfloxacin suspension

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different.     

Oral sustained delivery of atenolol from floating matrix tablets-formulation and in vitro evaluation

Floating matrix tablets of atenolol were developed to prolong gastric residence time and increase drug bioavailability. Atenolol was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The tablets were prepared by direct compression technique, using polymers such as hydroxypropyl methylcellulose (HPMC K15M, K4M), guargum (GG), and sodium carboxymethylcellulose (SCMC), alone or in combination, and other standard excipients. Tablets were evaluated for physical characteristics viz. hardness, swelling index, floating capacity, thickness, and weight variation. Further, tablets were evaluated for in vitro release characteristics for 8 hr. The effect of effervescent on buoyancy and drug release pattern was also studied. In vitro release mechanism was evaluated by linear regression analysis. GG- and SCMC-based matrix tablets showed significantly greater swelling indices compared with other batches. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium.