Sustained concentrations of active compound were maintained in vitro and in vivo for an oral and a parenteral dosage form respectively. The vehicle of a oral dosage form was modified and the molecular structure of a parenteral dosage form was modified. An oral dosage form was tested in vitro using dissolution apparatus. A parenteral dosage form was tested in vivo using rats. A new oral suspension dosage form for acetylsalicylic acid was compared to two controlled release forms and two immediate release dosage forms which are currently commercially available. A parenteral thrombomodulin analogue conjugated to polyethylene glycol was compared to the unconjugated thrombomodulin analogue. In each case the goal was to maintain sustained concentrations of active compound. / Graduation date: 1991

The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.

No description available.

No description available.

Graduation date: 1995

Gastrointestinal (GI) transit data were collected using pigs as animal models. Density and size effects of non-disintegrating dosage forms on GI transit were investigated. Total GI transit times range from 2 to 33 days for 22 administrations of these nondisintegrating dosage forms. Pigs are found to not be an appropriate animal model for studying bioavailability or GI transit of non-disintegrating, non-erodible oral release dosage forms. Development of controlled release dosage forms where the mechanism of drug release is diffusion through polymeric membrane formed via film coating utilizing fluid-bed technology requires optimization of several processing and formulation variables. The influence of a processing variable (nozzle orifice opening) and a few formulation variables (individual vs. combination plasticizer, or a water-insoluble additive) on dissolution of a model drug (acetaminophen) spray coated with Aquacoat® were studied. Pharmacodynamic and pharmacokinetic information for a model drug (acetaminophen) and computer simulation were used to develop a dosage form with a 12 hour sustained release for oral administration to children and adults for maximum analgesic and antipyretic effect. Simulated plasma acetaminophen concentration-time curves were similar to observed bioavailability study profiles. In vitro and preliminary in vivo results from an adult human volunteer indicate that sustained therapeutic saliva acetaminophen concentration is possible using the newly developed acetaminophen molded tablet dosage form. The bioavailability of the new, oral controlled release acetaminophen molded tablet relative to a commercially available product (Extra-Strength Tylenol® caplet) was evaluated in 8 healthy, adult volunteers. Multiple doses of these two products were administered in a two-way cross-over design. Bioavailability of the new sustained release molded tablet is comparable to that of the immediate release product. Polymer coated acetaminophen beads were effective in maintaining saliva acetaminophen concentrations of 5 μ/ml over a 12 hour dosing interval. / Graduation date: 1991

No description available.

No description available.

This dissertation describes the development of a new sustained release formulation of nifedipine. The new formulation was developed by coating commercially available immediate release soft elastic gelatin capsules using a spray coating technique with two different polymeric combinations. Dissolution studies were conducted and showed that controlled release of nifedipine was obtained by increasing the ratio of the water insoluble polymer in the coat and increasing the percent weight gain of the coating. Simulated plasma concentration versus time profiles after administration of 30 mg dose of selected formulations showed a prolonged nifedipine release with concentrations above the minimum effective concentration for up to 12 hours. Bioavailability and bioequivalence of tableted test formulation of verapamil HCL was determined in 8 volunteers and compared to Covera HS® under fed and fasting conditions. The 90% confidence intervals for individual percent ratios of the Cmax, AUC₀₋₅₈ and AUC₀ were not within the range of 80 - 125% in both fed fasted states, suggesting that these formulations are not bioequivalent. the bioavailability of verapamil from the new formulation was higher state but this effect was not statistically significant. Pharmacokinetics of terbinafine administered orally at single doses of 15, 30, 60 and 120 mg were determined in raptors to recommend an appropriate dosing scheduled for terbinafine in the treatment of Aspergillosis. Calculation of steady state trough terbinafine plasma concentration after administration of daily doses of 15 or 30 mg/day showed that 30 mg daily dose of terbinafine administered orally in raptors produces a steady state trough terbinafine plasma concentration above the minimum inhibitory concentration (MIC) of(0.8 1.6) µg/ml against aspregillus fumigatus. From the data, 30 mg per day oral dose of terbinafine should be the recommended dose for treatment of aspergillosis in raptors. Approximate pharmacokinetic linearity of terbinafine was demonstrated for AUC[subscript 0-t] in the dose range of 15 120 mg while non-linearity for Cmax in the same dose range was demonstrated using the power model. / Graduation date: 2005

No description available.