Biomedical subjects

S R Vaithiyalingam

Publications and source records attributed to S R Vaithiyalingam.

8 recordsLinked to original sources

PubMed2002

Formulation and stability evaluation of ketoprofen sustained-release tablets prepared by fluid bed granulation with Carbopol 971P solution.

The objectives of the present study were: (1) to investigate the possibility of using a Carbopol polymeric solution as granulating agent by the fluid bed granulating process; (2) to select a suitable method of tabletting for sustaining the release of ketoprofen for 12 hr; (3) to perform stability studies according to International Committee on Harmonization (ICH) guidelines and photostability on ketoprofen SR tablets; (4) to study the influence of the storage conditions on release kinetics and melting endotherm of ketoprofen; and (5) to predict the shelf-life of the ketoprofen SR tablets. Tabletting ingredients were ketoprofen, anhydrous dicalcium phosphate, Carbopol 971P, talc, and magnesium stearate. Carbopol 971P solution (0.8% w/v) was used as a granulating solution in the fluid bed granulator. For comparative evaluation, tablets were also prepared by direct compression and wet granulation, and subjected to dissolution. Tablets prepared by fluid bed granulation technique were stored in incubators maintained at 37, 40, 50, and 60 degrees C, 40 degrees C/75% RH, 30 degrees C/60% RH, and 25 degrees C/60% RH, and in a light chamber with light intensity of 600 ft candle at 25 degrees C. Melting endotherms were obtained for the drug as well as the tablets during stability studies by differential scanning calorimetry. Tablets prepared by fluid bed granulation technique prolonged the release of ketoprofen better than tablets obtained by direct compression and wet granulation. Further, it complied with the requirements of ICH guidelines for stability testing. Higher temperature and humidity (40 +/- 2 degrees C/75% RH, 40 degrees C, 50 degrees C, and 60 degrees C) adversely affected the rate and extent of the dissolution. Ketoprofen SR tablets stored in amber-colored bottles demonstrated a good photostability for 6 months at 600 ft candle. The shelf-life of the formulation was predicted as 32 months.

Acrylic Resins↗

PubMed2001

Design, in vitro stability, and ocular hypotensive activity of t-butalone chemical delivery systems.

The objective of this work was to synthesize two bioreversible diacyl derivatives of t-butalone (chemical delivery systems), determine their chemical and in vitro stability, and investigate their potential use as topical antiglaucoma agents. The stability of these compounds was determined in isotonic phosphate buffers (pH range 5-8) and in selected biological media, including human whole blood, rabbit and rat blood, and the anterior segment tissues of rabbit. The ocular hypotensive activity of these compounds in unrestrained, normotensive albino rabbits was determined with a pneumatonometer. The two compounds were stable at lower pH. The stability decreased as the pH increased, suggesting their lability to base-catalyzed hydrolysis. These compounds exhibited significant differences in the hydrolytic rates in the whole blood among species examined (rat > rabbit > human). The observed rates of disappearance in different ocular tissues were indicative of relative enzyme activity in these media (iris-ciliary body > cornea > aqueous humor). The two compounds exhibited a significant ocular hypotensive activity (P < 0.01) at 2% dose level. The peak activity was found between 2 and 4 h, and the activity was maintained for 4.5 to 7 h. The dipivalyl derivative of t-butalone exhibited more pronounced decrease in intraocular pressure than that of diisovaleryl derivative. The present study suggests the possible use of diacyl derivatives of t-butalone as ocular hypotensive agents.

Animals↗

PubMed2001

Intraocular pressure-lowering activity and in vivo disposition of dipivalyl terbutalone in rabbits.

The ocular hypotensive activity and in vivo disposition of dipivalyl terbutalone, a chemical delivery system for terbutaline, were investigated in the albino rabbit model. The dose-response relationship was assessed at drug concentrations ranging from 0.5 to 4% in normal saline. Intraocular pressure (IOP)-lowering activity of dipivalyl terbutalone was compared with epinephrine in equal concentrations. The in vivo disposition was investigated after topical administration of dipivalyl terbutalone at 4% dose level for which two metabolic products, terbutaline, and terbutalone, were monitored in different anterior segment tissues/fluid of albino rabbits, including corneal and iris-ciliary body homogenates and aqueous humor. The instillation of 0.5, 1, 2, and 4% solutions (1 drop of 50 microL) significantly decreased the IOP of normotensive rabbits in a dose-dependant manner. At the highest dose, the maximum reduction (5.6 +/- 0.65 mm Hg) was observed at 3 h. In a comparative efficacy study, dipivalyl terbutalone was found to be more effective than epinephrine. In the in vivo distribution after the topical administration of dipivalyl terbutalone, terbutaline was found only in the iris-ciliary body, whereas terbutalone was found in all parts of the eye studied. This work suggests the potential use of dipivalyl terbutalone as an antiglaucoma agent, representing a new chemical delivery system for terbutaline.

Administration, Topical↗

PubMed2001

Long-term stability characterization of a controlled release gastrointestinal therapeutic system coated with a cellulose acetate pseudolatex.

The objective of the present study was to study the long term effects of storage of osmotically controlled gastrointestinal therapeutic system (GITS) in exaggerated conditions of temperature and humidity. Bilayered osmotic tablets were obtained with atenolol, Polyox N80, Carbopol 934P and magnesium stearate in one layer, and Polyox 303, Carbopol 974, sodium chloride and magnesium stearate in the other layer. A customized cellulose acetate (CA) pseudolatex was used to provide semipermeable housing around the tablet and an orifice was drilled into the drug layer to obtain the Atenolol GITS. The GITS were stored at 4 degrees C (refrigeration), 25 degrees C, 37 degrees C, 45 degrees C, 55 degrees C, 37 degrees C/11% RH, 37 degrees C/51% RH, and 37 degrees C/91% RH. Quantitative X-ray diffraction and dissolution studies were performed at regular intervals for one year. Aqueous CA polymeric film formation continued in GITS stored at higher temperature by gradual evaporation of moisture and coalescence of polymer. At lower temperatures atenolol crystallinity increased with time, but at higher temperatures the crystallinity was decreased. At higher humidity, a decrease in crystallinity was observed. A decrease in dissolution rate and extent was observed at higher temperature and higher humidity conditions. Exaggerated temperature and humidity conditions affected the dissolution profile by modifying the CA pseudolatex membrane and crystallinity of atenolol.

Adrenergic beta-Antagonists↗

PubMed2001

Naproxen-Eudragit microspheres: screening of process and formulation variables for the preparation of extended release tablets.

The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on the rate of drug release. The response variable was cumulative percent of naproxen dissolved in 12 h in simulated intestinal fluid with constraints on responses that included percent yield, hardness, thickness, and the angle of repose. Mathematical relationship for percent of naproxen dissolved in 12 h (Y5) with various factors yielded the following polynomial equation; Y5 (% dissolved in 12 h) = 95.48 + 0.53 X1 + 3.51 X2 + 3.84 X3 - 3.80 X4 - 2.46 X5 - 2.90 X6 - 3.91 X7. The results showed that all the seven factors affected, with varying order, the release of naproxen from its compressed tablets.

Acrylic Resins↗

PubMed2000

Captopril gastrointestinal therapeutic system coated with cellulose acetate pseudolatex: evaluation of main effects of several formulation variables.

Maintenance of constant drug levels in the body for those drugs that are used in management of hypertension is extremely beneficial. This can be successfully achieved by delivering the antihypertensives as osmotically-controlled drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the main effects of the formulation variables on the release of captopril from osmotically-controlled drug-delivery system coated with a custom-made cellulose acetate (CA) pseudolatex reported earlier. A secondary objective was to identify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (> or = 90% intact captopril) in solution in the presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Plackett-Burman screening design was employed to study the main effects of amounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulative percent of drug released in 12 h, Y(3), with constraints on lag time Y(1) and time for 50% drug released Y(2)amount of sodium chloride (1.97).

Algorithms↗

PubMed2000

Stability characterization of controlled release coprecipitates and solid dispersions.

The present study was conducted to determine the effects of ageing at exaggerated storage conditions on controlled release tablets prepared with indomethacin-Eudragit((R)) coprecipitates (CPs) and solid dispersions (SDs). CPs and SDs compressed as tablets were stored at -20, 4, 37, 45, 55, 37 degrees C/11% RH, 37 degrees C/51% RH and 37 degrees C/91% RH. The samples were analyzed over a period of six months for their dissolution, crystalline reversion and thermal changes. Samples stored at extremely low temperatures, higher temperatures and humidity conditions exhibited a significant decrease in dissolution rates. However, no significant change in the release rates was observed for samples stored at 4 degrees C. The degree of crystallinity increased over a period of time as confirmed by X-ray diffractometry. DSC data demonstrated that indomethacin exists in two polymorphic forms, Form I (mp 160-161 degrees C) and Form II (mp 153-154 degrees C). CPs showed an endotherm of Form I, whereas SDs showed a mixture of Form I and II.

Acrylic Resins↗

PubMedDate not supplied

Response surface methodology to obtain naproxen controlled release tablets from its microspheres with Eudragit L100-55.

PURPOSE: Naproxen CR tablets have been obtained from its microspheres prepared by coprecipitation with Eudragit L100-55. The purpose of this work was to evaluate the main and interaction effects of deaggregating agent concentration (X1), compression pressure (X2) and amount of precipitating water (X3) on naproxen release. A secondary purpose was to obtain an optimized naproxen controlled release solid oral dosage form with a predictable 12 h drug release. METHOD: Eudragit L100-55 (10 g) was dissolved in 100 ml of ethyl alcohol, and 30g of naproxen was dispersed in it with stirring. Purified water (100mL, cooled to 4 degrees C) containing calcium chloride as a deaggregating agent was added to an alcoholic solution and homogenized. The mixture was filtered to obtain microspheres. Drug content analysis was performed spectrophotometrically at 332 nm. Tablets were prepared by compressing microspheres containing 500mg of naproxen after adding 1% magnesium stearate. Dissolution was performed by the USP specifications of naproxen tablets. A 3-factor 3-level Box-Behnken design was employed to get 15 experimental runs. The independent variables used were X1, X2 and X3. The dependent variables were dissolution at different time points with constraints on yield value and angle of repose of the microspheres, and hardness and thickness of the tablets. The dissolution constraints were placed such that the naproxen is released for 12 h by Higuchi's square root of time kinetics. RESULTS: The mathematical relationship obtained between X1, X2, X3 and the cumulative per cent of naproxen dissolved in 12 h with various constraints (Y5) was Y5 = 92.39 - 1.13X1 - 4.84X2 - 2.12X3 - 2.26X1X2 - 0.5X1X3 - 0.4X2X3 + 2.4X(1)(2) - 0.4X(2)(2) (R2 = 0.9). The equation shows that X1, X2 and X3 affected the release inversely, and the most significant interaction was between X1 and X2. Y5 has been maximized for optimization of naproxen release. CONCLUSIONS: Controlled release tablets of naproxen with predictable drug release characteristics were obtained by compressing its microspheres with Eudragit L100-55.

Anti-Inflammatory Agents, Non-Steroidal↗