Terry D. Wilson

Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound.

Self-emulsifying drug delivery systems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsifi-cation was studied using a laser diffraction sizer to determine particle size distributions of the resultant emulsions. An optimized formulation which consisted of 25% (w/w) surfactant, 40% (w/w) oil, and 35% (w/w) WIN 54954 emulsified rapidly with gentle agitation in 0.1 N HCl (37°C), producing dispersions with mean droplet diameters of less than 3 µm. The self-emulsifying preparation was compared to a polyethylene glycol 600 (PEG 600) solution formulation by administering each as prefilled soft gelatin capsules to fasted beagle dogs in a parallel crossover study. Pharmacokinetic parameters were determined and the absolute bioavailability of the drug was calculated by comparison to an i.v. injection. The SEDDS improved the reproducibility of the plasma profile in terms of the maximum plasma concentration (Cmax) and the time to reach the maximum concentration (tmax). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations.

Analysis of Barbiturate Mixtures Using HPLC with Diode Array Detection

Abstract A study has been conducted on the HPLC analysis of barbiturate mixtures in which coeluting components with similar UV spectra could be distinguished by diode array detection. Mixtures containing phenobarbital and barbital in combination from about 0.25 to 0.00025 mg/mL each were measured using the spectral overlay, absorbance ratio, peak maximum absorbance and purity parameter techniques. The most sensitive of the standard methods available was absorbance ratio plotting in which the presence of 0.0125 mg/mL barbital could be distinguished from phenobarbital at 0.2375 mg/mL.

Recent Advances in HPLC Analysis of Analgesics

Abstract Recent developments in HPLC analysis of analgesics have been rapid, paralleling the growth of chromatographic sciences as a whole. Although analgesics have been used for hundreds of years and chromatgraphic separations have been carried out on them for decades, liquid chromatographic analysis of analgesics has advanced most rapidly in the past 5–7 years . The present review will focus on applications of HPLC to the analysis of commercial analgesics in this time period with emphasis on novel developments and applications associated with the improved accuracy, sensitivity and specificity in herent in current LC systems.

Structural influences on the amperometric detection of opiates in high-performance liquid chromatography

The oxidation reactions of a series of opiates occurring at a glassy-carbon electrode in amperometric high-performance liquid chromatographic detection has been investigated. A structure-reactivity correlation has been drawn for morphone, morphinan and benzomorphan derivatives. Polarography and hydrodynamic voltammography were used to show the importance of phenolic groups to this reaction. Acyl substitution on the phenol did not prevent amperometric detection.

High-performance liquid chromatographic-amperometric determination of naloxone hydrochloride injection

Naloxone hydrochloride has been measured in the injectable dosage form at 0.4 and 0.02 mg/ml using high-performance liquid chromatography with amperometric detection. This method was contrasted with an ultraviolet detection method at 229 nm and found to provide comparable recovery and linearity results. At the electrochemical detection limit of 0.1 ng injected a signal-to-noise ratio of 10.4 was found.

HPLC Determination of Lactic Acid in Milrinone Injection and Oral Solution Using Ion-Exchange Sample Preparation Methods

Abstract Lactic acid has been measured in Milrinone Injection and Oral Solution by HPLC using an ion-exclusion polymeric column coupled with a reversed-phase guard column. This dual-column chromato-graphy was preceded by classical ion-exchange sample preparation to eliminate interfering excipient components. The lactic acid lactate content of USP lactic acid was converted to lactic acid in processing. It was also further characterized using a TLC separation.

Sample solvent effects in an apparent chiral high-performance liquid chromatographic separation on β-cyclodextrin

Abstract The effect of sample solvent on chromatographic peak shape using a β-cyclodextrin column has been investigated. Sample solvents ranging in polarity from hexane to mobile phase (water-methanol-0.5 M pH 4.5 borate buffer, 600:400:1) were used with assessments of column efficiency made by calculating theoretical plates as N 5 σ , N 4 σ and N SYS . Best agreement with observed peak shape resulted from use of N 5 σ especially in the narrow polarity span from 40 to 100% methanol. No chiral separation was obtained on the cyclodextrin column for the aminoalkylindole compounds investigated, although one possessed a naphthaldehyde substituent which should have promoted such separation.

Pentazocine tablet analysis using high-performance liquid chromatography

Abstract A rapid extraction ion-pair reversed-phase system has been demonstrated for analysis of pentazocine hydrochloride in tablets. This high-perfromance liquid chromatographic method was also shown to separate other members of a series of benzomorphans. A favorable comparison was found between results by this method and a normal-phase HPLC method for pentazocine. The effects of ion-pairing agent and of concentration were investigated in view of possible retention mechanisms. A review of previous analytical methods for pentazocine is given.

High-performance liquid chromatographi determination of tornalate® in solution dosage forms; a specificity study

A reversed-phase high-performance liquid chromatographic method has been applied utilizing ion-pairing to measure Tornalate in solution dosage forms. Specificity of the method was demonstrated by selectivity for Tornalate analysis, analysis of stressed samples and by peak homogeneity tests. These included the diode-array derived spectral overlay test and fraction collection with rechromatography in an alternate normal phase system. Linearity was also demonstrated in terms of recovery from synthetic samples and detector response.

Validation of an amperometric high-performance liquid chromatographic determination of epinephrine in bupivacaine and epinephrine injection

Epinephrine, as the bitartrate salt at a 1:200000 dilution is contained in the 0.5% bupivacaine HCl, 2-piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride monohydrate. The development and validation of a sensitive and specific stability-indicating high-performance liquid chromatography (HPLC) assay method utilizing amperometric detection was desired as an improvement over and simplification of previous methods for epinephrine in this product