PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “BIOPHARMACEUTICS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,711 records · Page 95Linked to original sources
PubMed1979

Improvements of dissolution characteristics and chemical stability of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester by cyclodextrin complexation.

Inclusion complexation of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (I), which is effective in early pregnancy termination, with cyclodextrins in water was ascertained by a solubility study. A solid complex of I-beta-cyclodextrin in a 1:2 molar ratio was obtained, and its dissolution behavior and chemical stability were examined. The results indicated that the complex may have great utility as a rapidly dissolving form of I with prolonged storage time.

Biopharmaceutics↗
PubMed1981

Thermodynamic dependence of interfacial transfer kinetics of nonionized barbituric acid derivatives in two-phase transfer cell.

A theory was developed to describe interfacial transport kinetics of a series of drug homologs in a two-phase transfer cell. When tested, the theory held true for 5,5-disubstituted barbituric acid derivatives in a preequilibrated octan-1-ol = (pH 5) aqueous buffer system maintained at 37 degrees and stirred symmetrically at 50 and 100 rpm. Theoretical prediction of transfer kinetics was not possible in such a cell if the phases were stirred asymmetrically. For symmetric stirring, successful prediction of the transfer kinetics of any homolog in the series was possible from a knowledge of the partition coefficient and transfer kinetics of the parent compound, the partition coefficient of the homolog, and some easily determined system variables. The viscosity and density of the two phases and the phase-volume ratio were needed to define a system constant dependent on the solute diffusion coefficient, interfacial area, donor phase volume, and the boundary layer thickness for diffusion in the donor phase volume, and the boundary layer thickness for diffusion in the donor phase. A method is described to enable estimation of this constant from a knowledge of the transfer kinetics of the parent compound. The rank order of compounds in terms of their observed first-order transfer rate constants is shown to be dependent on the characteristics of the solvent system and stirring conditions employed, as well as on the physical chemistry of the solutes. The results are discussed in light of previously documented investigations.

Barbiturates↗
PubMed1985

Steady-state bioavailability of dexbrompheniramine and pseudoephedrine from a repeat-action combination tablet.

The steady-state bioavailabilities of dexbrompheniramine and pseudoephedrine were evaluated following multiple-dose administrations of a repeat-action combination tablet containing 6 mg of dexbrompheniramine maleate with 120 mg of pseudoephedrine sulfate every 12 h for 7 d compared with reference standards. The reference standards used in this study were concomitant administration of conventional 2-mg dexbrompheniramine maleate tablets every 4 h and 120-mg pseudoephedrine sulfate repeat-action tablets every 12 h, each for 7 d. Twelve healthy adult male volunteers completed this randomized two-way crossover study. Blood samples for subsequent assay were obtained at frequent time intervals throughout each 7-d dosing phase. Sensitive and specific gas-liquid chromatographic methods were used for the determination of dexbrompheniramine and pseudoephedrine in plasma. Based on the plasma levels, the times to reach steady state were determined. In addition, the major bioavailability parameters (Cmin, Cmax, tmax, and AUC) for days 6 and 7 of dosing were determined and statistically evaluated. The results of this study demonstrate that, at steady state, the repeat-action combination tablet and concomitant administration of the reference standards are bioequivalent.

Biological Availability↗
PubMed1985

Topical carbonic anhydrase inhibitors IV: Relationship between excised corneal permeability and pharmacokinetic factors.

Ethoxzolamide (1) and two analogues, representing a hydroxyethoxy and a hydrogen substitution on the 6-position of the benzene ring (2 and 3), were applied to rabbit eyes using a topical infusion method designed to provide a constant rate into aqueous humor. Statistical-moment theory was applied to the topical infusion data to describe disposition of each compound within the rabbit eye. For each analogue, it was possible to compare the corneal absorption rate constant (ka), aqueous humor elimination rate constant (k10), disposition mean residence time (MRTd), apparent steady-state volume of distribution (Vdss), and total ocular clearance (Qe). In vivo ocular ka values were related to maximum in vitro corneal penetration rates determined across excised rabbit corneas. In particular, 2 had a much longer residence time and a slower clearance than 1 and 3, which may be responsible for its ability to lower intraocular pressure when dosed topically to the rabbit eye, whereas 1 and 3 show no activity.

Administration, Topical↗
PubMed1989

Numerical stability of pharmacokinetic deconvolution algorithms.

The sensitivity of pharmacokinetic deconvolution algorithms with respect to simulated experimental error has been studied. Approximations of cumulative absorption profiles reconstructed from simulated data sets with normally distributed random error were compared with corresponding known input functions. The coincidence of both functions was assessed in 600 numerical experiments by the nonparametric Kolmogorov-Smirnov test. A constrained iterative nonlinear regression procedure based on the analytical convolution of multiphasic zero-order input functions with linear disposition models was found to perform well under conditions where the results of direct numerical deconvolution and model-based mass balance methods were unsatisfactory.

Absorption↗
PubMed1995

Spinal controlled delivery of bupivacaine from DL-lactic acid oligomer microspheres.

Bupivacaine-loaded microspheres made from DL-polylactic acid oligomers of different molecular weights (MW 2000 and 9000 g/mol, named PLA 2000 and PLA 9000, respectively) which displayed different in vitro release profiles were administered via the spinal route to rabbits. In comparison to the drug administered as a solution (2 mg as equivalent base), PLA 2000 and PLA 9000 microspheres (10 mg as equivalent base) led to a slower uptake of the drug in the systemic circulation, as suggested by the mean maximal plasma concentrations: 326 +/- 81, 321 +/- 57 and 64 +/- 54 ng/mL, respectively. Pharmacodynamic evaluation of the anesthetic action, by means of intensity and time course of motor blockade, indicated a sustained release. In comparison to the drug solution, the PLA 2000 microspheres led to an increase duration of median maximal blockade (172 min versus 44.5 min). The PLA 9000 microspheres failed to reach maximal blockade as a result of a too low release rate.

Animals↗
PubMed1995

Biophysical models as an approach to study passive absorption in drug development: 6-fluoroquinolones.

A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described. A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples. Equations based on two classic biophysical absorption models are given for predicting the intrinsic absorption features of the series according to the partition data or merely single structural parameters. In situ absorption rate constants were found to increase by a factor of 9.7-13.5 for moderately lipophilic derivatives relative to the simplest compound, while antibacterial activity decreased only by a factor of 4. In vivo absorption tests with two representative members of the series were carried out and the results showed a good accordance with those found in situ. This makes these compounds or related ones with similar partition features excellent candidates for further pharmacokinetic and pharmacological testing. The study can serve as an example of how to prevent potential absorption problems associated with the development of new drugs.

Administration, Oral↗
PubMed2002

Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process.

Throughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra-fast gradient chromatographic methods. Typical ultra-fast high-performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full-linear gradients over 1-2 min at very high flow rates (1.5-2 mL/min) on very short HPLC columns (2 x 20 mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn-around time. Some examples of this approach are discussed in further detail.

Animals↗
PubMed1991

On the estimation of total variability in assay validation.

In the pharmaceutical industry, an assay method is considered validated if the accuracy and precision for an assay meet some acceptable limits. This paper discusses the assessment of assay precision in terms of the estimation of total variability of an assay from a one-way random effects model which is often considered in assay validation. We propose a general class of estimators that includes the analysis of variance estimator and the maximum likelihood estimator. We derive the optimal estimator, in terms of smallest mean squared error, within this class and consider an approximate version of this optimal estimator. We report on a Monte Carlo simulation to study its finite sample performance. We also present two examples to illustrate the use of the proposed methodology.

Analysis of Variance↗
PubMed1999

Open questions on bioequivalence: some problems and some solutions.

This paper focuses on some specific situations where bioequivalence requires careful attention and tailored protocols in order to overcome intrinsic difficulties either marginally covered or fully neglected by operating guidelines. Some problems congregate with serious difficulties, namely high variability, very poorly absorbed drugs and endogenous substances with their own baseline. With endogenous substances, the dilemma faced is whether to subtract baseline from post-dose values in assessing bioequivalence. Either approach has intrinsic problems and is somewhat puzzling. In an attempt to resolve other existing problems, the most appropriate approach should be selected on a case-by-case basis, ensuring that the adopted procedure does not conflict with operating guidelines and scientific literature on the matter. Problematic cases include the management of trials with a predominant active metabolite, the absence of a reliable analytical bioassay, the availability of various strengths of the same drug on the market, a wide acceptability titre range, the management of studies on topical drugs that are devoid of systemic activity, the management of drugs that cannot be given for ethical reasons to healthy subjects or that may cause adverse events, especially when a steady state design is required. The parallel group study design appears to be more appropriate than the cross-over or the individual bioequivalence design in assessing drugs with a long half-life. Some pharmacokinetic and statistical analysis-related issues are also discussed such as the sequence/period interaction sometimes encountered in these trials, which, in the absence of the carry-over effect, does not bias the bioequivalence results and the need to process data with non-compartmental pharmacokinetic analysis.

Biopharmaceutics↗
PubMed2006

Filter construction and design.

Sterilizing and pre-filters are manufactured in different formats and designs. The criteria for the specific designs are set by the application and the specifications of the filter user. The optimal filter unit or even system requires evaluation, such as flow rate, throughput, unspecific adsorption, steam sterilizability and chemical compatibility. These parameters are commonly tested within a qualification phase, which ensures that an optimal filter design and combination finds its use. If such design investigations are neglected it could be costly in the process scale.

Biopharmaceutics↗
PubMed2006

Microfiltration membranes: characteristics and manufacturing.

Membrane filtration is used within a multitude of processes ranging from dialysis to desalination processes to sterilizing filtration in the pharmaceutical industry. Membranes, nevertheless, have to have special characteristics and properties to serve such specific applications. Microfiltration membranes are utilized in a large range of membrane polymers and structures, which all have individual production process steps to achieve consistently the same membrane parameters. This chapter discusses membrane polymers and production processes in detail.

Biopharmaceutics↗
PubMed2006

Filter validation.

Validation of a sterilizing filtration process is critical since it is impossible with currently available technology to measure the sterility of each filled container; therefore, sterility assurance of the filtered product must be achieved through validation of the filtration process. Validating a pharmaceutical sterile filtration process involves three things: determining the effect of the liquid on the filter, determining the effect of the filter on the liquid, and demonstrating that the filter removes all microorganisms from the liquid under actual processing conditions.

Bacteria↗