Degradation kinetics of thiamine hydrochloride in directly compressed tablets iii water vapour transmission through free and applied eudragit films

Abstract

Water vapour transmission through free and applied film of four Eudragit resins namely, E₁₀₀, L₁₀₀ and RS₁₀₀ to directly compressed thiamine hydrochloride tablets was investigated. The type of Eudragit film influenced both water vapour transmission and moisture absorption characteristics of the tablets compressed with either single or binary blend of vehicles. The moisture absorption rate constant K_a, for a given batch was found to be a function of vapour pressure, P, and film thickness, L. The relationship between K_a and either of these parameters is exponental and may be expressed as K_a = A exp (x/P) and K_a = K*_a exp (-x*L). In general, film coating with Eudragit resins affected the physical characteristics of the tablets. The rate of drug release, K has an exponentially relationship as K_e K_o exp (-c/L).     

The Effect of Polymer Coating Systems on the Preparation, Tableting, and Dissolution Properties of Sustained-Release Drug Pellets

The preparation of sustained-release (SR) drug pellets and their tablets was evaluated. Pellets containing indomethacin, pseudoephedrine hydrochloride (P-HCl), or pseudoephedrine (P) base were prepared by spraying a mixture of drug, Eudragit S-100 resins, dibutyl sebacate, and alcohol onto nonpareil seeds via the Wurster-column process. The oven-dried drug/Eudragit S-100 (DS) pellets were coated with different levels of Eudragit RS and Eudragit S-100 acrylic resins. Tablets containing P-HCl or P-base SR pellets, microcrystalline cellulose, and Methocel K4M were compressed. The solubility of the drug entity in the polymer solution was found to be the most critical factor affecting the yield and the physical properties of the resultant DS pellets. Dissolution studies of Eudragit RS coated drug pellets demonstrated that the release profiles depended not only on the physicochemical properties of the drug, particularly aqueous solubility, but also on the coating levels. The release rate profiles of the matrix tablets can be modified by varying the types of P-HCl or P-base SR pellets in the formulation. The release of drug from the matrix tablets is primarily matrix controlled.     

Controlled Release Salbutamol Sulphate Molded Tablets Using Eudragit Retard

Permeable acrylic resins were used as efficient retarding materials to prepare controlled release salbutamol sulphate molded tablets. The formulation is simple, efficient, economic and is easily shaped into molded tablets. The effects of two types of acrylic resins, namely: Eudragit RL100 ad Eudragit RS100 in concentrations 1, 2 and 5% w/w on the physical characteristics as well as on the in vitro release patterns of salbutamol sulphate from molded tablets prepared with either polyethylene glycol (PEG) 4000 or 6000 were studied. It was revealed that, as the molecular weight of the PEG increased, the hardness of the tablets increased. Considerable retardation in the drug release was observed by using Eudragit RS100 as compared to Eudragit RL100. The formulation prepared with PEG 6000 and 5% Eudragit RS100 produced much more release time prolongation than the other tested formulations. On the other hand, tablets prepared by the direct compression technique produced a faster release of salbutamol sulphate than those prepared by molding.     

Controlled Release Salbutamol Sulphate Molded Tablets Using Eudragit Retard

Abstract

Permeable acrylic resins were used as efficient retarding materials to prepare controlled release salbutamol sulphate molded tablets. The formulation is simple, efficient, economic and is easily shaped into molded tablets. The effects of two types of acrylic resins, namely: Eudragit RL100 ad Eudragit RS100 in concentrations 1, 2 and 5% w/w on the physical characteristics as well as on the in vitro release patterns of salbutamol sulphate from molded tablets prepared with either polyethylene glycol (PEG) 4000 or 6000 were studied. It was revealed that, as the molecular weight of the PEG increased, the hardness of the tablets increased. Considerable retardation in the drug release was observed by using Eudragit RS100 as compared to Eudragit RL100. The formulation prepared with PEG 6000 and 5% Eudragit RS100 produced much more release time prolongation than the other tested formulations. On the other hand, tablets prepared by the direct compression technique produced a faster release of salbutamol sulphate than those prepared by molding.     

Polymers with pH-dependent solubility: possibility of use in the formulation of gastroresistant and controlled-release matrix tablets

Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.     

Polymers with pH-Dependent Solubility: Possibility of Use in the Formulation of Gastroresistant and Controlled-Release Matrix Tablets

Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.     

Preparation and Dissolution Characteristics of Prolonged Release Mebeverine-HCL Beads

Different batches of slow release mebeverine-HCl beads were prepared by pan coating technique using different release retarding polymers viz Eudragit RL₁₀₀, Eudragit RS₁₀₀ and Ethyl cellulose. The thickness of the coats was controlled by changing the amounts of the added polymers. Pre- and overcoating of the beads with bees wax was also carried out. Mixtures of pre-waxed Eudragit RS₁₀₀ coated and uncoated beads in different ratios were prepared to control both drug content and release.

Dissolution profiles of mebeverine HCl from the prepared beads were investigated using USP XX rotating basket method. Prolonged release of mebeverine-HCl was obtained from different batches of the coated beads with the advantage of no initial dumping of the water soluble drug. The release of mebeverine-HCl from the beads coated with acrylic resins and ethyl cellulose as well as waxed acrylic resins coated beads was diffusion controlled according to Higuchi model. Beads coated with ethyl cellulose showed a different release pattern when pre-or overcoated with wax. By altering the ratios of prewaxed Eudragit Rs₁₀₀ coated and uncoated beads in formulated mixtures, it was possible to control both mebeverine-HCl content and release rate.     

Evaluation of Thermal and Film Forming Properties of Acrylic Aqueous Polymer Dispersion Blends: Application to the Formulation of Sustained-Release Film Coated Theophylline Pellets

Abstract

Aqueous acrylic polymer dispersions were blended in order to improve processing and film formation from acrylic polymers with poor film forming properties and/or to obtain sustained-release film coated pellets with optimal barrier properties according to the physicochemical and pharmacokinetic requirements of the active substance.

Heterogeneous film structures are generally obtained from blends containing an association of hard acrylic polymers (Eudragit* RS30D, S100) with the soft Eudragit* NE30D when the drying temperature is lower than the minimum film forming temperature (MFT) of the hard acrylic polymers. The Tg and MFT values of the hard acrylic polymers are not modified in the presence of the soft polymer as shown by the thermograms of these blends which are generally characterized by two individual glassy transitions.

On the other hand, a wide range of drug dissolution profiles can be obtained from film coated pellets either by using, in different proportions, the insoluble but readily permeable Eudragit* RL30D in association with the less permeable Eudragit* RS30D in order to obtain pH-independent permeability membrane, or by mixing the anionic methacrylic acid copolymers (L30D, S100) with the neutral NE30D in order to obtain pH-dependent permeability film coated pellets showing higher dissolution release rates at intestinal pH values.     

IR spectra and etch rates of plasma-enhanced chemically vapour-deposited phosphosilicate glass films

IR transmission spectra of phosphosilicate glass (PSG) films with 8 wt.% P prepared by plasma-enhanced chemical vapour deposition (PECVD) and CVD are compared. The differential IR spectrum of a PECVD PSG film differs from that of a CVD PSG film: the P=O peak has a lower intensity than the corresponding peak of the CVD film with the same phosphorus content; no peaks are evident at 980 and 500 cm⁻¹—the characteristic frequencies for P---O---P stretching and bending vibrations. The differential IR spectra of PECVD and CVD PSG films become very similar after annealing for 4 h in water vapour at 850°C. The etch rate of a PECVD film in p-etchant, which is constant throughout the film thickness, is 400 Å min⁻¹. However, the etch rate recorded after the film is subjected to annealing in water vapour at 850°C varies with the depth in the film, attaining values as high as 800 Å min⁻¹ in the region near the outer surface of the film. The results are explained as due to the oxidation of P₂O₃ to P₂O₅.     

Compression of Indomethacin Coprecipitates with Polymer Mixtures: Effect of Preparation Methodology

The objective of this study was to prepare, characterize, formulate and compare coprecipitates, solid dispersions and physical mixtures of indomethacin with Eudragit polymer mixtures, RS100 and L100. Coprecipitates, solid dispersions (melting-solvent method) and physical mixtures were prepared with a drug : polymer ratio of 12.6: 1.0 respectively. Biconvex tablets of 7 mm diameter were compressed. Response variables studied were cumulative percent released and T₅₀. Dissolution was performed by exposing the tablets to SGF (PH 1.2) for 1 hour followed by pH 7.2 phosphate buffer for 24 hours. T₅₀ values obtained were 7.5 hours for coprecipitates, 4.5 hours for solid dispersions and 17 hours for physical mixtures. The drug loading for all the three formulations did not show significant difference. The formulations were characterized by X-ray diffraction (qualitative and quantitative) and IR. IR data did not indicate any significant difference between the pure drug and the formulations. However, significant differences were seen in X-ray diffractograms. The crystallinity did not change for physical mixtures, was reduced for coprecipitates and solid dispersions. Also the diffraction patterns for solid dispersions and coprecipitates were similar. The coprecipitates and physical mixture followed the Higuchi's square-root-of-time equation suggesting a matrix effect. These results suggest that compression of coprecipitates offer most efficient release as compared to solid dispersions and physical mixtures.     

Preparation and In-Vitro Evaluation of Prolonged Release Tablets of Pheniramine Aminosalicylate

Prolonged release tablets of pheniramine aminosalicylate were prepared from co-precipitates of the drug in different types of Eudragit. The hardness of the tablet had a pronounced effect on the release rate of the drug. Tablets (500 mg, hardness 13 kg) and 375 mg tablets (hardness 6.5 kg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100, and 20% of the drug in Eudragit S 100 respectively, showed release rate patterns that were in agreement with Lang primary requirements for drug release from sustained release tablets.

Tablets (500 mg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100 or Eudragit S 100 and 375 mg tablets containing 20% of the drug in Eudragit S 100 showed release rate patterns that were best described by Higuchi equation, indicating that a diffusion controlled mechanism was mainly operative.     

A pH-dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. II. Manipulation of drug release using Eudragit L100 and Eudragit S100 combinations

Tablets containing mesalazine as a model drug were coated using various combinations of two methacrylic acid copolymers, (Eudragit® L100 and Eudragit S100) by spraying from aqueous systems. The Eudragit L100-Eudragit S100 (w/w) combinations studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5, and 0:1. The coated tablets were tested in vitro for their suitability for pH-dependent colon-targeted oral drug delivery. The dissolution profiles of the drug obtained from the studied tablets demonstrate that the release of the drug could be manipulated by changing the Eudragit L100-Eudragit S100 ratios in the combinations within the pH range between 6.0 and 7.0 in which the individual polymers are soluble, and a coating formulation consisting of a combination of the two polymers can overcome the issue of high gastrointestinal (GI) pH variability among individuals. The results also demonstrate the feasibility of using aqueous dispersions of Eudragit L100-Eudragit S100 combinations for coating tablets for colon-targeted delivery of drugs, and that the formulation can be adjusted to deliver drug(s) at any other desirable site of the intestinal region of the GI tract in which pH of the fluid is within the range 6.0 to 7.0. For colon-targeted delivery of drugs, the proposed combination system is superior to tablets coated with either Eudragit L100 or Eudragit S100 alone.     

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.     

Effective Intestinal Absorption of Insulin in Diabetic Rats Using Enteric Coated Capsules Containing Sodium Salicylate

Abstract

The absorption of insulin manifested as percent reduction of blood glucose was evaluated after placement of capsules containing 4.6 units of the drug and 20 mg of Sodium salicylate as an absorption promoter in the rate stomach. The capsules were coated with either Eudragit L100 or Eudragit 9100 to deliver insulin in different regions of small intestine of the rats as they are pH dependent. The data obtained after administration of the capsules were compared with that after intraperitoneal injection of 1 U of insulin and ALSO after administration of coated capsules containing insulin alone. The administration of insulin capsules containing sodium salicylate result in a significant (p<0.01) increase of the hypoglycemic effect over the 5 h period of the experiments. They produced the same hypoglycemia effect as I.P. injection at 5 h point. The areas under the % blood glucose reduction curves produced were 363.5, 221.7 and 236.5% h for I.P. injection and capsules coated with Eudragit L100 and Eudragit S100, respectively. The relative bioavailabilities of capsules to I.P. injection were 13.26 and 14.15% for those coated with Eudragit L100 and Eudragit S100, respectively. Enteric coated capsules of insulin alone caused no glucose reduction.     

The Influence of Drug-Excipient and Drug-Polymer Interactions on Butt Adhesive Strength of Ranitidine Hydrochloride Film-Coated Tablets

ABSTRACT

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.     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Ontrolled-Release Theophylline Tablet Formulations Containing Acrylic Resins. I. Dissolution Properties of Tablets

The dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from Theodur^R (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin.     

Effects of Annealing on the Conductivity of C60 Thin Films

Films of C₆₀, at different stages of annealing of T_t=200°and 300°C have been electrically characterized over the temperature domain from -130°C to T_t. X-ray diffraction revealed a random polycrystalline fee structure with stacking defects of an intrinsic nature, due to deposition conditions. The value of room-temperature conductivity was found to be in the range (6.3-1.0) *10^-10 (0cm)^-1. In the stable annealed state the conductivity showed an activated temperature dependence above 423 K and a non-activated dependence below 330-280 K. The activation energies E_a = 0.8 eV (film thickness 0.70 μm) and E_a = 1.0 eV (film thickness 2.40 μm) were in good agreement with the energy gap values (1.63 eV and 2.08 eV) which were deduced from the absorption spectral dependence. Annealing decreased the non-activated contribution to conduction, extending the intrinsic conduction temperature range.     

The photoresponse of high resistance anatase TiO2 films prepared by the decomposition of titanium isopropoxide

High resistance films of the anatase phase of TiO₂ have been prepared by spray pyrolysis starting with titanium isopropoxide Ti(OPrⁱ)₄. The films were deposited on glass substrates held at 590 K. The TiO₂ films were characterized structurally, optically, and electrically. The photoresponse of these films to prolonged UV radiation in a vacuum and subsequently subjected to O₂, H₂, water vapour, or air environments, has been investigated. When vacuum, O₂ or air is present, the electrical and optoelectronic properties observed can be explained by the induced variations in the oxygen deficiency at the surface of the TiO₂ film and the resulting formation or removal of an enhancement layer at the surface. An equivalent effect on the surface band bending can be induced by an absorbed species. For example, adsorbed water vapour can alter the surface conductance of the films and the result depends on the oxygen-to-titanium ratio present at the surface when the water vapour is introduced.     

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins, II. Combination Resin Formulations

Theophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness between the range of 6.8 kg to 15 kg showed minimal influences on the dissolution rate. Recompression and relubrication of the tablet formulation containing both polymers, produced a decrease in release rates of theophylline from the tablet matrix.