No description available.

Rheological characterization of pharmaceutical semisolids is of importance as it provides fundamental information required for the assessment of some of the final properties of a product such as viscosity, elasticity, quality and storage stability. The effect of formulation variables on product characteristics such as consistency and correlation of consumer evaluation of consistency can also be attained. (Ramachandran et al., 1999) This study focussed on using rheological techniques to fully characterize the properties of various semisolid formulations being developed or produced at a South African-based generic pharmaceutical company. Various tests were employed to characterize the semisolid dosage forms (creams and ointments), including continuous shear tests such as flow and viscosity curves and yield point measurements, oscillatory tests such as amplitude and frequency sweeps, as well as step and temperature ramp tests. A method to determine justifiable and meaningful viscosity specifications was developed, where excellent reproducibility of results were obtained when compared to the single-point viscosity determinations usually used. An evaluation as to whether rheology can be utilized as an assessment tool for product stability revealed varying results, with the oscillation-frequency sweep test displaying modest predictive capabilities. Observable differences in rheological character were found when evaluating ointment formulations exhibiting deviating quality characteristics. When analysing the effect of varying processing parameters, namely, cooling rate and mixing speed, during the manufacture of a cream, statistically significant rheological differences were obtained, while a thorough characterization of a scale-up procedure was also achieved upon analysis of various rheological properties.

No description available.

No description available.

The investigations in this dissertation have been 'conducted to investigate the formulation and analysis of a paediatric amoxycillin suppository. The oral administration of antibiotics to young children can at times be roblematic. Compliance is sometimes poor because of a sore throat, nausea, vomiting, a high fever or a dislike for the taste or smell of the medicine:- In-such cases the rectal administration of an antibiotic could provide an alternative route of administration that avoids some of the problems that affect oral administration. Difficulties associated with rectal administration are bioavailability, local irritation, acceptability to patients and rejection of the dosage form. Few data, however, are available on the usefulness in children of suppositories in general, and antibiotic suppositories in particular. The areas of investigation have included the formulation of an amoxycillin suppository in various fatty bases, the quantitation of amoxycillin in both aqueous solution and human serum, assessment of stability of amoxycillin in stored aqueous and biological samples, in vitro drug release testing of suppositories, and bioavailability and pharmacokinetics following administration to human subjects of capsule, suppository, oral suspension and rectal suspension dosage forms. Suppositories containing 250 mg amoxycillin were prepared in theobroma oil and in the semisynthetic bases Witepso[ W35, Suppocire A32, Novata BD and Novata 299. The in vitro release characteristics of amoxycillin from these lipophilic suppository formulations were investigated using the USP rotating basket method. The dissolution of a drug from a solid dosage unit is an important parameter affecting drug bioavialability. High Performance Liquid Chromatography (HPLC) was used as the main analytical technique. An original HPLC method for analysis of amoxycillin in aqueous solution, using ultraviolet detection at 230 nm was develcfped. The validated method was a~plied to the determination of the stability of aqueous amoxycillin solutions, and was utilized to determine the amount of drug released during dissolution testing. Differential scanning calorimetry (DSC) is a technique commonly used in preformulation studies. Dissolution testing was used in conjunction with DSC to select a suppository base suitable for formulation with amoxycillin trihydrate. An HPLC method for analysis of amoxycillin in human serum using UV detection at 230 nm is presented. The method involves a solid phase extraction procedure followed by chromatography on a reversed phase column. The limit of sensitivity of 0.3 ILg/mL in serum is sufficiently sensitive to monitor serum concentrations of amoxycillin in humans after the administration of a single 250 mg oral dose. Pharmacokinetic parameters were calculated from data obtained following the administration of a capsule and oral suspension. These parameters were consistent with previously published results. Following administration of a lipophilic suppository and a rectal suspension, to human volunteers, it was concluded that amoxycillin trihydrate is not readily absorbed from the rectum. Further investigations into the modification of the suppository dosage form with absorption enhancers to improve rectal absorption of amoxycillin, as well as elucidation of the mechanism of absorption of the drug, could assist in improving this formulation so that it is suitable for paediatric use.

University of Macau / Institute of Chinese Medical Sciences

Part I. Following a general historical review of the development of drug targeting, critical evaluations were made of current targeted drug delivery systems. Based on the results shown by previous studies, magnetic albumin microspheres containing adriamycin is one of the most promising targetable delivery systems for the treatment of solid tumors. It was also apparent that the pharmacokinetics of drugs associated with magnetic albumin microspheres had not been determined. A systematic study of the multiple variables involved in albumin microsphere preparation was completed to identify to what extent these variables affected the microsphere size distribution. The results of this investigation led to an optimal method of microsphere preparation. Information obtained from the above studies was applied to the production of magnetic albumin microspheres containing adriamycin suitable for in vivo use. The problems of separation and quantitation of adriamycin and adriamycinol in biological matrices were investigated using ion-pairing high pressure liquid chromatography. An optimized chromatographic system was presented for the analysis of these compounds in rat serum and tissues. The disposition of adriamycin following administration as magnetic albumin microspheres and as a solution was studied by monitoring adriamycin concentrations in multiple rat tissues for forty-eight hours after administration. The magnetic dosage form was targeted to a predefined tail segment with a magnetic field strength of 8000 G applied for 30 min after dosing. A physiological pharmacokinetic model was used to describe the disposition of adriamycin after both dosage forms. The model developed following adriamycin administration as a solution served as the foundation for the model for adriamycin when it was administered as the magnetic dosage form. Part II. The present investigation was designed to characterize the kinetics of ibuprofen in plasma and synovial fluid, which in the past, has been flawed by inadequate study protocols. After administration of a single dose and at steady-state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. The extent of accumulation of ibuprofen in each fluid was determined. The degree of ibuprofen protein binding in plasma and synovial fluid was also determined and related to its kinetic behavior.

No description available.

No description available.

Thesis (MAppSc in Pharmacy)--University of South Australia, 1996