methylcellulose and acetylcellulose

This study investigates the effects of supercritical CO

Topics: Carbon Dioxide; Cellulose; Drug Compounding; Itraconazole; Methylcellulose; Solubility; Succinates

The focus of this work was to explore feasibility of using blends of cellulose esters (CA 320S, CA 3980-10 or CAB 171-15) and enteric polymers (C-A-P, Eudragit® L100 or HPMCP HP-55) for delayed and enteric coating of tablets containing either diclofenac sodium (DFS, high dose) or prednisone (PDS, low dose) drug. The core tablets of DFS or PDS were coated with polymer blends to achieve approximate weight gain of 5% and 10%. The coated tablets were characterized for dissolution (0.1 N HCl and phosphate buffer pH 6.8) and surface morphology. The surface morphology of CA 398-10 or CAB 171-15 based polymer blends was rough and fibrous. Less than 0.5% drug was dissolved in 120 min from 5% w/w coated tablets in acid-phase dissolution testing. The dissolution in phosphate buffer pH 6.8 medium varied from 16.2 ± 0.2 to 98 ± 2.1%, and 30.1 ± 0.5% to 101.7 ± 3.4% in 120 min from DFS and PDS coated tablets, respectively. Dissolution was less in CA 320S based blends compared to CA 398-10 or CAB 171-15 blends in phosphate buffer medium. Furthermore, there were no significant differences observed in dissolution profiles of coated tablets of DFS or PDS. This can be explained by dose of the drugs. Additionally, dissolution was higher in tablets coated with enteric polymer alone compared with the blends. In conclusion, core tablets can be coated with cellulose ester and enteric polymers blend to impart both delayed and enteric release feature to the tablets containing hydrophilic or hydrophobic drug.

Topics: Cellulose; Diclofenac; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Methylcellulose; Polymethacrylic Acids; Prednisone; Tablets, Enteric-Coated

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs.

Topics: 2-Propanol; Calorimetry, Differential Scanning; Cellulose; Chemistry, Pharmaceutical; Citrates; Delayed-Action Preparations; Drug Carriers; Glipizide; Hydrodynamics; Hydrogen-Ion Concentration; Hypoglycemic Agents; Hypromellose Derivatives; Kinetics; Methanol; Methylcellulose; Models, Chemical; Osmosis; Poloxamer; Polymers; Porosity; Powder Diffraction; Solubility; Solvents; Surface-Active Agents; Technology, Pharmaceutical; Temperature; Water; X-Ray Diffraction

Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diclofenac; Excipients; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Kinetics; Lactose; Membranes, Artificial; Methylcellulose; Microscopy, Electron, Scanning; Osmosis; Plasticizers; Polyethylene Glycols; Porosity; Potassium Chloride; Sodium Chloride; Solubility; Surface Properties; Tablets; Technology, Pharmaceutical; Triacetin

The objective of this study was to demonstrate that the asymmetric membrane capsule can be used to deliver a poorly water soluble drug with a pH dependent solubility such as atenolol for extended periods of time by modulating solubility with organic acid. In osmotic systems, the release rate of an excipient relative to the release rate of the drug is an important factor that determines the duration of drug release. Consequently, for maintaining the desired pH over the entire period of drug dissolution a suitable thickening and suspending agent can be incorporated. By optimizing the concentration of thickening agent, it is possible to extend the availability of pH modifier in the core to provide an osmotic driving force or solubilization over the entire delivery period, so that the desired profile can be achieved for an active agent that has lower solubility characteristics. Finally, it was observed that the release rate of atenolol was influenced by the concentration of citric acid, mannitol and hydroxypropyl methylcellulose (HPMC). Results of scanning electron microscopy studies showed the formation of pores in the membrane from where the drug release occurred. The optimal formulation was found to be able to deliver atenolol at the rate of approximate zero-order up to 24 h, independent of pH of release media and agitation rate.

Topics: Atenolol; Capsules; Cardiovascular Agents; Cellulose; Citric Acid; Delayed-Action Preparations; Diffusion; Drug Compounding; Drug Delivery Systems; Excipients; Hydrogen-Ion Concentration; Hypromellose Derivatives; Kinetics; Mannitol; Methylcellulose; Microscopy, Electron, Scanning; Solubility; Surface Properties; Viscosity

The present work investigates the feasibility of the design of a novel floating elementary osmotic pump tablet (FEOPT) to prolong the gastric residence of a highly water-soluble drug. Diethylcarbamazine citrate (DEC) was chosen as a model drug. The FEOPT consisted of an osmotic core (DEC, mannitol, and hydrophilic polymers) coated with a semipermeable layer (cellulose acetate) and a gas-generating gelling layer (sodium bicarbonate, hydrophilic polymers) followed by a polymeric film (Eudragit RL 30D). The effect of formulation variables such as concentration of polymers, types of diluent, and coat thickness of semipermeable membrane was evaluated in terms of physical parameters, floating lag time, duration of floatation, and in vitro drug release. The Fourier transform infrared and X-ray diffraction analysis were carried out to study the physicochemical changes in the drug excipients powder blend. The integrity of the orifice and polymeric film layer was confirmed from scanning electron microscopy image. All the developed FEOPT showed floating lag time of less than 8 min and floating duration of 24 h. A zero-order drug release could be attained for DEC. The formulations were found to be stable up to 3 months of stability testing at 40°C/75% relative humidity.

Topics: Acrylic Resins; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diethylcarbamazine; Drug Compounding; Drug Stability; Excipients; Feasibility Studies; Humidity; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Kinetics; Mannitol; Methylcellulose; Microscopy, Electron, Scanning; Osmosis; Permeability; Plasticizers; Powders; Sodium Bicarbonate; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; Tablets; Technology, Pharmaceutical; Temperature; Water; X-Ray Diffraction

Osmotic delivery systems are based on osmotic driving force. Nifedipine tablets, available under the trade names Procardia XL (Pfizer) and Adalat (Bayer), are commercialized drug-delivery systems of an elemental osmotic pump that the push-pull osmotic tablet operates successfully in delivering water-insoluble drugs. For the improvement of the release pattern and the solubility of the drug, we developed a squeeze-type osmotic tablet (SQT) for nifedipine as a model drug. The SQT was composed of one or more ring type of squeeze-push layer (squeeze-disc) and a centered drug core. Squeeze-discs were stacked up with different physicochemical properties with gradient such as viscosity, swelling ratio and water absorption ratio using the osmotic agents from a disc of bottom to top. The present work investigated the effect of different preparation factors, such as hydrophilic polymers, the molecular weight of polymers, coating process, orifice size and types of excipient on release performance of nifedipine. With the purpose of delivering water-insoluble nifedipine at an approximate zero-order rate and step-function rate for 24 h, SQT has been successfully prepared, and significantly improved in the release rate and patterns in comparison with the Adalat push-pull system in vitro release features.

Topics: Cellulose; Delayed-Action Preparations; Hypromellose Derivatives; Membranes, Artificial; Methylcellulose; Molecular Weight; Nifedipine; Osmosis; Osmotic Pressure; Polyethylene Glycols; Polyvinyl Alcohol; Potassium Chloride; Sodium Chloride; Tablets; Triacetin

Oral osmotic devices including an elementary osmotic pump (EOP) are efficient systems for the delivery of drugs with high/moderately water-solubility. In this study we designed a new type of EOP for the efficient delivery of poorly water-soluble and practically insoluble drugs. In this system, called swellable elementary osmotic pump (SEOP), drug is released from the delivery orifice in the form of a very fine dispersion of drug in gel which is ready for dissolution and absorption. Factors affecting the release of drug from the SEOP containing a poorly water-soluble drug, nifedipine, were explored extensively. To this end, effect of swelling and wetting agents, orifice size, concentration of osmotic agent, and hydrophobic plasticizer were investigated. Interestingly, in the absence or low concentration of a hydrophobic plasticizer (caster oil), the osmotic devices did not retain their integrity in dissolution media. Caster oil in concentration of > 1% was necessary for tablets to retain their integrity during dissolution process. A zero-order release kinetics for nifedipine was achieved following the effective optimization of the concentrations of swelling agent, osmotic agent, wetting agent, and also size of orifice and membrane thickness in SEOP. The zero-order release lasted for 10 hr at pH 6.8 dissolution medium. The designed SEOP is suggested as an efficient controlled delivery system for oral delivery of a poorly water soluble drug such as nifedipine.

Topics: Administration, Oral; Castor Oil; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Gels; Hydrogen-Ion Concentration; Hypromellose Derivatives; Kinetics; Membranes, Artificial; Methylcellulose; Models, Chemical; Nifedipine; Osmosis; Permeability; Plasticizers; Potassium Chloride; Sodium Dodecyl Sulfate; Solubility; Tablets; Water; Wetting Agents

The objective of this study was to investigate the use of water soluble cellulose acetate (WSCA) as a film coating material for tablets. Aspirin (ASA) tablets were prepared by direct compression and coated with either WSCA or HPMC (hydroxypropyl methylcellulose) dispersions. Coatings of 1-3%, depending on the intended application, were applied to the model drug (ASA) tablets employing a side-vented coating pan. Free films of WSCA, prepared by cast method, are crystal clear and, depending on the viscosity grade, are flexible, strong and durable. WSCA has the capability of forming free films without plasticizers and the films dry at room temperature. Glass transition temperature, Tg, was determined by differential scanning calorimetry. The Tg of WSCA is significantly higher relative to HPMC. Inclusion of plasticizer lowers the Tg of WSCA and effective plasticizers were PEG 400 and glycerin. Low viscosity WSCA was more soluble in water (25-30%) relative to medium viscosity WSCA (10-15%). WSCA solutions exhibited no increase in viscosity with an increase in temperature. Samples of coated (WSCA and HPMC) tablets and uncoated ASA cores were packaged for stability studies at room and elevated temperature storage. Physical stability of ASA tablets coated with 2:1 LV: MV (low viscosity: medium viscosity) WSCA formulations was better when compared to tablets coated with HPMC. Dissolution stability of WSCA coated ASA was similar to the physical stability results. After three months at elevated temperature (35 and 45 degrees C), the WSCA coated tablets complied with USP dissolution requirements for ASA, while the HPMC coated tablets did not. There was no difference in moisture (weight) gain of ASA tablets coated with either WSCA or HPMC. The WSCA coated tablets were not sticky or tacky, while the HPMC coated tablets were tacky and stuck together.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biocompatible Materials; Cellulose; Chemistry, Pharmaceutical; Drug Stability; Hypromellose Derivatives; Methylcellulose; Solubility; Viscosity

Diltiazem hydrochloride (DLTZ) is a freely water-soluble drug, because of its higher aqueous solubility, the suitability of the drug with elementary osmotic pumps is restricted. Plain DLTZ elementary osmotic pump had shown higher release rate. Drug entrapment in polymer matrix or addition of release retardant materials (various polymers) can reduce the release rate of drug. In present study, effect of appropriate hydrophilic polymers (HP) on the release pattern was investigated. Ingredients of the system were optimized for parameters like drug:polymer ratio and amount of osmogent, for the desired release pattern. Two optimized formulations were selected for further characterization. Theoretical release rate of the formulations were also determined and compared. Different dissolution models were applied to drug release data in order to establish release mechanism and kinetics. Criteria for selecting the most appropriate model were based on best goodness of fit and smallest sum of squared residuals.

Topics: Calcium Channel Blockers; Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Diltiazem; Drug Carriers; Excipients; Hypromellose Derivatives; Kinetics; Methylcellulose; Osmosis; Solubility; Technology, Pharmaceutical

The objective of this study was to compare the performance of cellulose acetate (CA) and ethylcellulose (EC)-HPMC combination coatings as semipermeable membranes (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions. Osmotic pump tablets were designed with different coating variables and optimized in terms of nature of plasticizer, membrane thickness, and orifice diameter. The effect of insertion of an inner microporous film around the NPS core to minimize deformation of the SPM due to peristaltic movement of the gut was also studied. Osmotic pump tablets composed of membranes with water-soluble plasticizer, propyleneglycol (PG), released drug mainly through diffusion, whereas those designed with CA and EC-HPMC (4:1) coats containing water-insoluble plasticizer, castor oil, released their contents by perfect zero-order kinetics over a prolonged period of time, though the average release rate that could be achieved with the EC-HPMC (4:1) membrane was only about half the rate achieved with the CA membrane for the same membrane thickness. Release rates for both the membranes decreased with increasing membrane thickness and were found to be independent of orifice diameter, agitation intensity, and pH of the dissolution medium.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Dosage Forms; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Naproxen; Osmosis; Permeability; Tablets

The purpose of the study was to develop a new three-dimensional model using force, time and displacement to characterize the densification behavior of tableting materials. Normalized time (x), displacement converted to ln(1/1 - D(rel)) according to Heckel (y) and force presented as pressure (z) were used to plot a graph. A twisted plane was fitted to this three-dimensional plot. This plane was characterized by three parameters d, the slope over time called 'time plasticity', e, the slope over pressure called 'pressure plasticity' and omega, the angle of rotation called 'fast elastic decompression'. These parameters were used to characterize the densification behavior of the well-known materials microcrystalline cellulose, dicalcium phosphate dihydrate, theophylline monohydrate, cellulose acetate and hydroxypropyl methylcellulose at different rho(rel, max). It could be shown that brittle, elastic and plastic compression properties could be very well distinguished and differentiated. Further on, it could be shown whether these properties were due to pressure or time. Thus this model has the prevailing advantage to characterize tableting materials in one step according to time and pressure and it is a useful tool to develop tablet formulations or new excipients.

Topics: Algorithms; Calcium Phosphates; Cellulose; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Models, Theoretical; Pressure; Tablets; Theophylline; Time Factors

The objective of this study was to develop and evaluate floating and pulsatile drug delivery systems based on a reservoir system consisting of a drug-containing effervescent core and a polymeric coating. Preliminary studies identified important core and coating properties for the two systems. The mechanical properties (puncture strength and elongation) of acrylic (Eudragit RS, RL or NE) and cellulosic (cellulose acetate, ethyl cellulose) polymers, which primarily determined the type of delivery system, were characterized with a puncture test in the dry and wet state. For the floating system, a polymer coating with a high elongation value and high water- and low CO(2) permeabilities was selected (Eudragit RL/acetyltributyl citrate 20%, w/w) in order to initiate the effervescent reaction and the floating process rapidly, while for the pulsatile DDS, a weak, semipermeable film, which ruptured after a certain lag time was best (ethyl cellulose/dibutyl sebacate 20%, w/w). With the floating system, the polymeric coating did not retard the drug release. A polymer (cellulose acetate or hydroxypropylmethylcellulose) was added to the core to control the drug release. The time to flotation could be controlled by the composition (type of filler, concentration of effervescent agents) and hardness of the tablet core and the composition (type of polymer and plasticizer) and thickness of the coating. For the pulsatile system, a quick releasing core was formulated in order to obtain a rapid drug release after the rupture of the polymer coating. The lag time prior to the rapid drug release phase increased with increasing core hardness and coating level.

Topics: Cellulose; Drug Delivery Systems; Lactose; Methylcellulose; Oxazines; Plasticizers; Solubility; Time Factors

The effects of physical aging on the water permeation of cellulose acetate and ethylcellulose, the mechanical properties of ethylcellulose, and the dissolution property of hydroxypropyl methylcellulose phthalate were investigated. The water permeabilities of cellulose acetate and ethylcellulose and the dissolution rate of hydroxypropyl methylcellulose phthalate were found to decrease with physical aging time after being quenched from above the glass transition temperatures to sub-Tg temperatures. The gradual approach toward thermodynamic equilibrium during physical aging decreases the free volume of the polymers. This decrease in free volume is accompanied by a decrease in the transport mobility, with concomitant changes in those properties of the polymer that depend on it. The effects of long-term aging on the dissolution rate and water permeabilities of these polymers can be estimated from a linear double-logarithmic relationship between the mobility properties and physical aging time. The existence of the linear double-logarithmic relationship can be derived from the Williams-Landel-Ferry equation, the Doolittle equation, Struik's model, and Fujita's relationship between diffusion and free volume.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Methylcellulose; Permeability; Polymers; Solubility; Tablets; Temperature; Time Factors