Michael Makoid

The Routine Analysis of Breast Milk for Drugs of Abuse in a Clinical Toxicology Laboratory

Drug screening of breast milk in a clinical toxicology laboratory is reported. Findings from three cases include cocaine, ethylbenzoylecgonine (cocaethylene), ethanol, oxycodone, codeine, and nicotine. We believe this to be the first report of ethylbenzoylecgonine in human breast milk. One other specimen submitted for analysis was screened with negative results. Screening and confirmation procedures adapted for use with breast milk are described. Finally, the potential for cocaine intoxication from mother to baby is discussed. Estimates of infant blood cocaine concentration are given which may increase awareness of the need to monitor milk and blood cocaine concentrations in the infant when the situation warrants.

The design of flexible ciprofloxacin-loaded PLGA implants using a reversed phase separation/coacervation method.

The purpose of this research is to design and characterize flexible PLGA-based implants for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro. This research uses a reversed phase separation/coacervation method to fabricate flexible PLA and PLGA: excipient implants with dichloromethane/mineral oil as solvent/non-solvent. Physical characterization was performed using thermal and mechanical analyses. Drug loading and release studies were performed with ciprofloxacin HCl as the model drug. Release kinetics was modeled to elucidate possible mechanisms of drug release. Four polymer-excipient combinations with glass transition temperatures less than 20°C and representing a wide range of Youngs moduli were shown to entrap up to 8% of ciprofloxacin HCl that could be released at a controlled rate for 65 days in vitro. The release rate could consistently fit a ternary Gaussian pattern with an R(2)>0.99. It was postulated that these release patterns could be related to ciprofloxacin that was loosely or poorly bound (burst release), trapped within the polymer matrix, or encapsulated by the polymer. These studies show that flexible implants can be fabricated from PLGA-based polymers for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro.

The effect of coencapsulation of bovine insulin with cyclodextrins in ethylcellulose microcapsules

Polymeric microcapsules have been widely investigated for protein delivery. Common problems include: low stability, low encapsulation efficiency, lack of uniformity, and burst release. Cyclodextrins (CDs) are known to enhance stability and solubility of proteins in solution. This research examines the effect of α-, β-, and γ-CDs on: (1) stability, (2) encapsulation, and (3) release of insulin from ethylcellulose microcapsules. All CDs improved thermal stability of insulin by lowering the enthalpy of unfolding by 16–52%. α- and γ-CDs also increased the encapsulation efficiency of insulin and improved uniformity of the microcapsule formulations. Two mathematical models were proposed to account for insulin release and consisted of multiple zero order and first order input processes, and a single first order output process. All CDs decreased the initial burst release of insulin by up to 30%. This research demonstrates the potential for CDs to improve stability, uniformity, and encapsulation of proteins in microcapsule formulations.

Release Kinetics of Polymeric Prodrugs of Pindolol (PDL)

Various type of pendant chain polymeric prodrugs of pindolol were synthesized and their release characteristics were evaluated. Non linear regression analysis of various mathematical models indicated a best fit was obtained in all cases by a concomitant zero and first order release pattern. The effect of load (w/w pindolol) and backbone (polymer type) were studied. An increase on load in the high molecular weight dextran (T - 70) resulted in a proportional increase in fraction of release exhibiting first order kinetics and a proportional decrease in the zero order rate constant. Across the three polymers studied, a polymer with a large first order fraction also had a large zero order rate constant and a faster overall release pattern.

Stability of Amoxicillin Trihydrate Oral Suspension in Clear Plastic Unit Dose Syringes

AbstractThe stability of amoxicillin trihydrate oral suspension stored in clear plastic oral syringes was studied.Commercially available amoxicillin trihydrate powder for oral suspension was reconstituted according to manufacturers instructions and drawn into 5-mL clear polypropylene plastic oral syringes. The syringes were divided into groups and stored at 25, 40, 60 or 80°C. Powder from two additional lots was similarly reconstituted, packaged and stored at 80°C only to assess interlot variability. Immediately after reconstitution and at specified times during storage, three syringes at each storage temperature were removed and their contents analyzed for amoxicillin trihydrate concentration by a spectrophotometric assay.Samples stored at room temperature retained at least 90% of the initial amoxicillin concentration for at least 78 days. Samples stored at heated temperatures (40, 60, and 80°C) exhibited a first-order degradation process, with the concentration of amoxicillin decreasing to less than 90...