Effect of Storage on the Properties of Acetylsalicylic acid Tablets Coated with Aqueous Hydroxypropyl Methyl-Cellulose Dispersion

The objective of this study was to investigate whether the properties of acetylsalicylic acid tablets coated with aqueous hydroxypropyl methylcellulose dispersion using glycerol or polyethylene glycol 6000 as plasticizer change during storage at 25° or 40°C. Titanium dioxide was used as pigment. The tablets were coated in a fluid bed apparatus. The disintegration time and the release of acetylsalicylic acid during two hours were determined for both uncoated and coated tablets immediately after their preparation and after different storage periods.

When the tablets were stored at room temperature (25°C) the coat protected the core efficiently against changes in the measured parameters as compared with uncoated tablets. However, at higher temperature (40°C) some unfavorable phenomena occurred in the coat and after storage of 48 months, the disintegration time was longer and the dissolution of acetylsalicylic acid slower than from uncoated tablets. Polyethylene glycol was found to be a better protecting agent than glycerol.     

Effect of Storage Conditions on the Hardness,Disintegration and Drug Release from Some Tablet Bases

Abstract

The effect of storage at relatively high temperature and humidity on tablets prepared from different bases was studied for up to eight weeks. Drug release from tablets was followed by measuring the concentration of a marker (amaranth) in the dissolution medium. Lactose and mannitol based tablets showed an increase in hardness and disintegration time, and a decrease in the initial rate of drug release. Sorbitcl based tablets, stored under 50°C/50% relative humidity (R.H.), showed a decrease in hardness and slower disintegration and dissolution. When stored under 40°C/90% R.H., the tablets were completely deformed within three days. Tricalcium phosphate and cellulose-based tablets did not show any storage related changes in hardness, disintegration or drug release.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

Preparation and Evaluation of Directly-Compressed Indomethacin,Indomethacin Sodium and Indomethacin Meglumine Tablets

Abstract

A formula containing Compactrol, Ac-Di-Sol, Aerosil 200 and talc was used to prepare directly-compressed tablets of indomethacin and its sodium and meglumine salts. The prepared tablets were evaluated for uniformity of weight and thickness, hardness, friability and content uniformity. Each batch was then divided into two, one was coated with an opaque non-enteric film coat and evaluated for coat thickness uniformity. The dissolution rates of the uncoated and coated tablets and the effect of shelf-storage, at room temperature for 11 months, on drug contents were also studied. Indomethacin meglumine tablets showed the least relative standard deviation of weight and thickness. They exhibited acceptable uniformity of content and coat thickness, and the highest hardness-friability ratio. Also exhibited, uncoated and coated, the best in-vitro release of its drug contents and the maximal stability.     

The Effects of Heat and Desiccation Treatment on the Controlled Release Properties of Aqueous Silicone Latex Coated Tablets

Abstract

An aqueous based polymeric coating system, polydimethyl-siloxane elastomer latex, was employed to coat acetaminophen tablets. Drug release characteristics due to this polymer coating were monitored by in-vitro dissolution tests. It was found that heat treatment of the coating and the desiccation pretreatment significantly changed the drug release profiles compared to untreated, coated tablets. The slowest drug release rate was obtained by desiccating the coated tablets for 24 hours or more followed by heat treatment at 40°C for at least 4.5 hours. Rupturing of the coating layer during dissolution testing was observed only if the curing process was not utilized. As expected, drug released at a given time was inversely proportional to the coating thickness.     

Physical Properties and Stability of Diazepam and Phenobarbitone Sodium Tablets Prepared with Compactrol

Abstract

Compactrol as a newly introduced direct compressible vehicle was used for the preparation of Diazepam and phenobarbitone sodium tablets. Spray dried lactose and wet granulation technique were also employed to prepare these tablets for comparison. The effect of storage at 75% RH, at two temperature levels (25° and 45°) on the physical properties of these tablets was studied for 6 weeks. It was found that, there were an increase in tablet weight, thickness and friability per cent, while a significant decrease in hardness was observed. Tablets prepared with compactrol showed no significant changes in both disintegration and dissolution times, while tablets prepared with spray dried lactose showed a marked decrease in disintegration and dissolution times. On the other hand, tablets prepared by wet granulation showed a pronounced in crease in both disintegration and dissolution times.     

Storage Related Physico-Chemical Changes in Aspirin and Phenylbutazone Tablets Compressed With Different Initial Moisture Content

Abstract

The storage conditions as well as the compressional conditions of the aged tablets were found to have significant effect on their physico-chemical properties. In this study the changes in tablet weight, thickness, hardness, disintegration, drug release and drug content were evaluated for aspirin and phenylbutazone (pbz) tablets made with microcrystalline cellulose (MCC) and lactose bases. Tablets were made with different initial moisture content and stored at 40°C/90% relative humidity (R.H.). Tablet thickness was found, in general, to increase with storage, this increase was more prominent with aspirin. The increase in thickness was always accompanied with a decrease in hardness. There was a marked increase in disintegration time and decrease in dissolution rate of phenylbutazone tablets. This was more significant for the lactose based tablets, while, for aspirin tablets there was a negligible increase in both dissolution rate and the disintegration time. The present study indicated that incorporation of drugs in tablet bases has resulted in a different response towards storage     

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

Abstract

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

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

The Strength and Compaction of Millispheres: The design of a controlled-release drug delivery system for ibuprofen in the form of a tablet comprising compacted polymer-coated millispheres

Abstract

This paper reviews a case study of the design of a controlled-release drug delivery system for ibuprofen in the form of a tablet comprising compacted polymer-coated millispheres (multiparticulate pellets). The particular challenge was to prepare coated millispheres of ibuprofen (a high-dose drug) with the addition of minimal excipients so that the drug-release retarding polymeric membrane surrounding the millispheres remains intact during and after tablet compression, disintegration and release of the millispheres. The study included (a) the design of the uncoated core and its manufacture by wet massing, extrusion, spheronization and drying; (b) the coating of these millispheres with a range of possibly suitable polymers; (c) an assessment of the drug release profiles from these pellets; (d) the quantification by indentation rheology of the mechanical properties of the polymer films used to coat the spheres; (e) the measurement of the mechanical properties of individual uncoated and coated millispheres and f. the design, manufacture and evaluation of compressed tablets containing coated millispheres

The matching of millisphere and polymer mechanical properties was found to be essential in order to ensure minimal damage to the millispheres and the release of virtually intact coated spheres without destruction of their retarded drug-release characteristics. Aqueous polymeric dispersions which formed a film with similar elastic and tensile properties to the uncoated millisphere formulation resulted in the most satisfactory film coating for application to spherical particles which must withstand compaction. Those polymeric films exhibiting significantly greater resilience than the uncoated cores were inappropriate for the film coating of millispheres for compaction into tablets     

Effects of Tablet Core Dimensional Instability on the Generation of Internal Stresses Within Film Coats

Abstract

Dimensional changes of tablets compressed from maize starch were measured by means of a free-armature transducer rig under three possible simulated film coating conditions (30°C and 45%RH, 40°C and 33%RH, and 45°C and 20%RH) for one hour and then during re-equilibration to ambient temperature and relative humidity until no further significant changes were detected. It was found that these changes were normally greater at the stage of re-equilibration of the tablets to ambient conditions rather than at the stage of exposure itself. Tablet expansions were observed to be greatest in cores which had been exposed to higher temperatures and lower relative humidities. The volume increase of freshly coated tablets due to moisture uptake is of great interest since it may produce high internal stress within the coat and cause coating defects such as cracking, edge splitting and peeling and/or bridging of the intagliations. Estimates have been made to emphasise the importance of the role played by these volume increases on the total internal stress created within the film coat. Some practical implications to reduce the internal stress caused by swelling of tablet core is also discussed.     

Use of Powdered Solutions to Improve The Dissolution Rate of Polythiazide Tablets

Abstract

Solutions of polythiazide in polyethylene glycol 400 were admixed with microcrystalline cellulose (RC-591) and silica. The resulting free-flowing powder was incorporated into tablet formulations by direct compression.

The dissolution rates of polythizizde frm these tablets were significantly more rapid than from commercially available tablets. The stability of these tablets at 40°0C and high humidity was studied. The powdered solution formulas were also compared with a polythiazide dispersion in polyethylene glycol 6000 which exhibited an equally superior dissolution profile.     

Comparative Evaluations of Aqueous Film Coated Tablet Formulations by High Humidity Aging

Compressed tablets of ticlopidine hydrochloride were coated with three aqueous film coating formulations and aged under 95% relative humidity at 23° and 37°. The in vitro dissolution of the drug from tablets coated with the formulation containing polymethacrylic acid esters before aging was slower than the tablets coated with the formulations containing hydroxypropyl methylcellulose or ethylcellulose dispersion. On aging, the in vitro drug dissolution of the coated and uncoated tablets decreased and the decrease depended on the film forming excipient in the coating formulation and the temperature of aging. The tablets coated with the formulation containing polymethacrylic acid esters dissolved very slowly after aging. Higher moisture contents of the tablets after aging under 95% relative humidity at 23° compared to 37° resulted in a consistently lower tablet crushing strength. The tablets coated with the formulation containing 10% hydroxypropy1 methylcellulose showed a smaller decrease in the tablet crushing strength on aging compared to the other two formulations.     

Preparation and In-Vitro Evaluation of A Controlled Release Drug Delivery System of Theophylline Using An Aqueous Acrylic Resin Dispersion.

Abstract

Eudragit® E30D was utilized in conjunction with talc and xanthan gum to coat theophylline granules via a Wurster-type air suspension column. Since the resin is extremely tacky and cannot be used alone as a coating formulation, different amounts of talc and xanthan gum were incorporated into the Eudragit® E30D suspension to allow for coating of theophylline granules. The release profile of theophylline from the coated granules was found to be dependent on the ratio of the additives to the resin used in the coating suspension as well as on the coating level applied to the final product. A sample of theophylline granules coated with a film-coating suspension containing 1.5:1.0: :Talc: Eudragit® E30D resin (calculated on dry basis) exhibited a zero order release profile. However, the in-vitro release rates of this formulation decreased on storage. As the ratio of talc and Eudragit® E30D was changed to 1:1, the coated theophylline granules showed a release profile that remained unchanged even after exposure at room temperature, 30° C and 40° C for three months. A stable theophylline formulation was achieved by curing the coated product at 40°C for 24 hours.     

Effect of Crystallization of Theophylline on Physical Properties of Tablets

Abstract

Tablets containing anhydrous theophylline, a hygroscopic material such as magnesium chloride or potassium acetate, and other constituents were stored for 4 and 12 weeks under 90% relative humidity at 37°C. During storage, whisker-like crystals appeared on the surface of the tablets. The crystals were observed under a scanning electron microscope. Changes were found in the physical properties of these tablets: crushing strength, friability, disintegration time and dissolution rate.     

Comparative Aging Studies of Tablets Made with Diabasic Calcium Phosphate Dihydrate and Spray Dried Lactose

Abstract

There are relatively few published reports on the aging of tablets (1-4) and thus, as an extension of previously published work, the aging of compressed tablets (prepared using either dibasic calcium phosphate dihydrate or spray^A dried lactose as matrix) has been investigated over a sixty-five day period. All tablets contained 6% amaranth as a dye tracer, 0.5% magnesium stearate as lubricant and 2.5% sodium alginate as disintegrant. Tablets were prepared by direct compression on a single punch press and stored under three sets of stress conditions: (a) 25°C, 45% relative humidity (RH); (b) 35°C, 60% RH; (c) 45°C, 75% RH.

Tablets were evaluated by appearance (visual and photography); weigh; size; hardness (Erweka); disintegration time (U.S.P.); and dissolution (U.S.P.). A transient mottling phenomenon was evident in both systems under accelerated conditions. Significant weight variations were observed at all temperatures for the dibasic calcium phosphate dihydrate system, while lactose tablets showed only slight changes in weight. Under accelerated storage conditions, hardness appears to be related to disintegration times and dissolution rates with either system. However, it is not a reliable tool at room temperature. In addition, results at accelerated conditions do not appear to be directly related to those obtained at room temperature.     

Prelimnaky Evaluation of Cissus Root Gum as a Binder in Sodium Salicylate Tablet Formulations

Abstract

Cissus root gum was processed and evaluated as a binder in lactose-based tablets each containing 100 mg of sodium salicylate as the active ingredient. Acacia binder was used as basis for comparison. Tablet hardness, friability, disintegration time and dissolution rate were the parameters investigated. The cissus gum gave hard and non-friable tablets at 1 - 3% w/w concentration of the tablet formula. Tablets containing above 2% w/w of the cissus gum gave high disintegration time values and the pattern of dissolution of the incorporated drug suggests that the gum may be useful in prolonged release tablet formulations. No significant changes in the tablet properties was observed after storage at 30°C for 16 weeks.     

Development of a Formulation of Sustained Release Potassium Chloride

Abstract

The purpose of this work has been the designing and “in vitro” evaluation of a potassium chloride tablet using a wax matrix.

Camauba wax, stearyl alcohol and stearic acid ware employed to prepare granulates at different drug/wax ratios. Fran dissolution kinetic studies and technological performances a 75/25 – KCl/camauba wax granulates was selected. The rheolqgical properties of granulates were characterized and tablets were manufactured employing ccrrmun tablets excipients. Also a coating procedure was developed. The coated tablet formulation selected release the potassium chloride according to the USP requirements.

The dissolution kinetics of the potassium chloride from both coated and uncoated tablets fit the Higuchi diffusion model, giving a straight line when the amount dissolved is plotted against the square root of time.     

Water Soluble Cellulose Acetate: A Versatile Polymer for Film Coating

ABSTRACT

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°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.     

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.     

Aqueous film coating to reduce recrystallization of guaifenesin from hot-melt extruded acrylic matrices

Objectives: This study investigated the effect of aqueous film coating on the recrystallization of guaifenesin from acrylic, hot-melt extruded matrix tablets. Methods: After hot-melt extrusion, matrix tablets were film-coated with either hypromellose or ethylcellulose. The effects of the coating polymer, curing and storage conditions, polymer weight gain, and core guaifenesin concentration on guaifenesin recrystallization were investigated. Results: The presence of either film coating on the guaifenesin-containing tablets was found to prolong the onset time of drug crystallization. The coating polymer was the most important factor determining the delay in the onset of crystallization, with the more hydrophilic polymer, hypromellose, having a higher solubilization potential for the guaifenesin and delaying crystallization for longer period (3 or 6 months in tablets stored at 40°C or 25°C, respectively) than the more hydrophobic ethylcellulose, which displayed a lower solubilization potential for guaifenesin (crystal growth on tablets cured for 2 hours at 60°C occurred within 3 weeks, whereas uncoated tablets displayed surface crystal growth after 30 minutes). Crystal morphology was also affected by the film coating. Elevated temperatures during both curing and storage, incomplete film coalescence, and high core drug concentrations all contributed to an earlier onset of crystal growth.