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At least 487 records · Page 27Linked to original sources
PubMed1990

Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs.

Absorption and disposition characteristics of carprofen were compared in the dog after intravenous, oral, and rectal administrations. Rectal formulations included an aqueous solution and a suppository. Single doses of 100 mg carprofen were given in a cross-over design and plasma concentrations of unchanged drug were determined by HPLC. Plasma concentration-time profiles could be adequately described after intravenous and extravascular administrations by tri-and biexponential functions, respectively. After intravenous applications the basic disposition parameters could be determined: mean (+/- S.D.) elimination half-life was about 11.7 (+/- 3.1) h; volume of distribution ranged from 0.12 to 0.22 l kg-1 and total plasma clearance was about 0.017 +/- 0.003 l h kg-1. After oral dosing, carprofen was rapidly absorbed (time of maximum concentration: 0.83 +/- 0.61 h) and comparison with the intravenous solution indicated complete bioavailability. After rectal administration, the rate of absorption evaluated through tmax and calculation of mean absorption times was always slower than after oral dosing. Relative bioavailabilities of the drug from the suppository were about 20 per cent lower than from rectal solutions. No significant difference in rates of absorption of carprofen from rectal solution and suppository was seen; this allowed the conclusion that drug release from the semi-solid dosage form was not the rate-limiting step in carprofen absorption from the suppository. From the present study, it is concluded that rectal administration of carprofen offers an alternative to the oral route of drug intake.

Administration, Oral↗
PubMed1993

Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol.

A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.

Administration, Buccal↗
PubMed2005

Implication of biopharmaceutics and pharmacokinetics of rifampicin in variable bioavailability from solid oral dosage forms.

Rifampicin is one of the oldest and most effective chemotherapeutic agents available for the treatment of tuberculosis but exhibits variable bioavailability from separate and fixed dose combination formulations, which has been identified as a major bottleneck in the effective treatment of tuberculosis. In this investigation, physico-chemical characterization, single dose pharmacokinetic studies and the permeability of rifampicin under physiological conditions in the rat were studied to trace the possible reasons for its variable absorption. Rifampicin exhibits very high solubility in acidic and basic pH, corresponding to the pH of the stomach and distal intestine, respectively, whereas it is moderately soluble at the jejunal pH. From single-dose pharmacokinetic studies and permeability characterization, rifampicin is a highly permeable molecule and thus according to BCS, it is a borderline class II drug. This investigation has ruled out the possibility of intrinsic solubility, effective permeability, drug decomposition, presystemic metabolism and interaction with other antituberculosis drugs as direct factors responsible for the variable bioavailability of rifampicin. However, it was found that the rate of dissolution in association with pH and the concentration-dependent absorption of rifampicin affects the in vivo performance of the dosage forms. In addition, this is the first report of methodology for correcting inlet concentration for permeability calculations of a chemically unstable molecule.

Animals↗
PubMed2002

Analysis of glycoproteins and the oligosaccharides thereof by high-performance capillary electrophoresis-significance in regulatory studies on biopharmaceutical products.

This review describes the recent development in the analysis of glycoproteins using capillary electrophoresis with various separation techniques, and focuses especially on the analysis of recombinant glycoprotein pharmaceuticals. We include the analysis of glycoprotein multiforms (ie glycoform) as well as glycan analysis. The relationship between glycoprotein multiforms and oligosaccharide distributions in a glycoprotein sample is also discussed. Further, recent development in capillary electrophoresis-mass spectrometry is described.

Carbohydrate Sequence↗
PubMedDate not supplied

Optimization of protein G chromatography for biopharmaceutical monoclonal antibodies.

Compared to more stable chromatographic media the use of affinity media with biological ligands such as Protein G Sepharose 4 Fast Flow poses special challenges regarding regeneration and sanitization. This is especially critical for the purification of pharmaceutical proteins, where complete regeneration of the column between runs is of paramount importance. Here, the problems encountered during process development and upscaling of regeneration methods for a Protein G Sepharose Fast Flow column intended for the large-scale purification of pharmaceutical monoclonal antibodies are reported. The initially chosen alkaline regeneration buffer led to an increase in the affinity of Protein G towards antibodies which made elution increasingly difficult. A combination of urea and acetic acid was selected to ensure efficient cleaning of the matrix without affecting ligand properties. Validation experiments were done to demonstrate the functional integrity of the matrix after repeated cycles of use and regeneration, as well as the efficiency of the cleaning process.

Antibodies, Monoclonal↗
PubMed2005

Biophysical signatures of noncovalent aggregates formed by a glucagonlike peptide-1 analog: a prototypical example of biopharmaceutical aggregation.

LY307161 is a 31 amino acid analog of glucagonlike peptide-1(7-37)OH susceptible to physical instability associated with pharmaceutical processing. Orthogonal biophysical studies were conducted to explore the origins of this physical instability and to distinguish pharmaceutically desirable states of this aggregating peptide from undesirable ones. Equilibrium sedimentation analysis established that LY307161 exists as a monomer at pH 3, and reversibly self-associates in the pH range 7.5-10.5. Causative factors for physical instability related to lyophilization conditions were investigated. Solution pH, acetonitrile content, and concentration of the peptide prior to lyophilization each impacted physicochemical properties of the resultant powders. A comparative study of two powder samples exhibiting physicochemically disparate properties established that LY307161 forms soluble noncovalent aggregates. FT-IR analyses in the solid and solution states identified a prominent band at 1657-1659 cm(-1) attributed to alpha-helix structure. Noncovalent soluble aggregate exhibited characteristic bands at 1615 and 1698 cm(-1) indicative of intermolecular beta-sheet structure. An agitation-induced, precipitated solid form of LY307161 exhibited a different FT-IR signature indicative of a conformationally distinct species. Circular dichroism and fluorescence spectroscopy, together with dynamic light scattering measurements and dye-aggregate complexation, provided additional insights into the distinctions between aggregated and native LY307161.

Biophysical Phenomena↗
PubMed1990

Biopharmaceutical evaluation of ketoprofen following intravenous, oral, and rectal administration in dogs.

The influence of the hydrophilicity of three suppository bases on the rectal absorption of ketoprofen was studied. Absorption characteristics of ketoprofen were compared after intravenous, oral, and rectal administrations of 100 mg of drug given in a crossover design to five dogs. Rectal formulations included an aqueous solution and three suppository formulations. After oral dosing, ketoprofen was rapidly absorbed (time of maximum concentration, tmax: 0.83 +/- 0.61 h), and a comparison with the intravenous solution indicated a complete bioavailability of 0.90 +/- 0.10. After rectal administration, the rate of absorption, as evaluated with tmax and mean absorption time, was always slower than after oral dosing. A high variability was observed in the plasma concentrations obtained with suppository formulations; bioavailability values were approximately 20% lower than those from the oral solutions. No statistical difference in bioavailability and peak concentrations between the three suppository formulations was observed. Time of peak concentrations, mean absorption times, and fractions of the dose absorbed 6 h post administration did not show a difference in rate of ketoprofen absorption from the three suppository formulations. This study did not reveal a relationship between rate and extent of ketoprofen rectal absorption and the hydrophilicity of the suppository bases tested.

Administration, Oral↗
PubMed2000

Biopharmaceutics of liposomal interleukin 2, oncolipin.

Oncolipin is a multilamellar liposomal (dimyristoyl phosphatidylcholine) formulation of interleukin 2 (IL-2) and human serum albumin (HSA) with distinct surface characteristics which may influence its biological activities. IL-2 and HSA were detected on the surface of the liposomes using specific antibody staining. Surface expression of IL-2 was also demonstrated by the observation that Oncolipin bound to cells expressing IL-2 receptors (IL-2R) containing alphabetagamma or betagamma subunits. Binding and internalization of Oncolipin by cells expressing alphabetagamma or betagamma receptor subunits was blocked by excess free IL-2 or a neutralizing antibody against the beta chain. The display of surface IL-2 on Oncolipin's liposomes was maintained in vivo after intravenous injection into mice. IL-2 was also present between the lipid bilayers of the multilamellar liposomes based on the unique physical characteristics detected by freeze fracture electron microscopy. The bulk of the liposome-associated IL-2 was released from the liposomes upon incubation at 37 degrees C in medium containing serum, indicating that the IL-2 was not irreversibly entrapped on or in the liposome structure. Thus, Oncolipin is receptor-targeted to activated T and NK cells by virtue of its surface expression of IL-2 and has the potential to release IL-2 following deposition within lymphoid organs. These properties may confer distinct advantages over soluble IL-2 for immunotherapy of cancer and viral diseases.

Animals↗
PubMed1980

MANOVA of statistical moments in biopharmaceutical studies: a numerical example with three equally spaced doses of amoxicillin.

To assess the applicability of statistical moments in biopharmacuetical studies, an urinary excretion trial was conducted with three doses--400, 500, and 600 mg of amoxicillin trihidrate capsules--in 15 healthy volunteers, using a latin square design. The statistical analyses were a two-way MANOVA and a growth curve technique. It was inferred, in the dose range studied, that the amount excreted during the 12 hr following administration, was proportional to dose and that the dose had no effect on either the mean or the variance of the residence time. The calculated minimum significant difference in the amount of amoxicillin excreted was 15% with respect to the mean value.

Absorption↗