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 55 records · Page 3Linked to original sources

PubMed1998

Identification and development of new biopharmaceuticals.

The 34 protein based biopharmaceuticals which are presently on the market reached a total sale of 10 Mio $ in 1996. Out of 500 biopharmaceutical under investigation, 200 are already in clinical trial programs. Although biopharmaceuticals have good records in efficacy and drug safety, biologics are still competitive due to economic reasons. In future in some cases gene therapy or oligonucleotide antisense therapy as modern technologies for in vivo protein synthesis regulation will be an alternative to protein replacement therapy. All three therapeutic approaches will be supported by the human genome project which will give new hints on genetic disorders related to specific diseases. The identification of new therapeutic developments will be on the DNA-, RNA- and protein level. The decision whether the therapeutic principle will be gene therapy or whether the differential genomic analysis will provide just a research tool for high through-put screening of small molecules will be decided upon the evaluation of the results of the genomic projects and the research strategy of the company.

Animals↗

PubMedDate not supplied

Bioanalytic considerations for pharmacokinetic and biopharmaceutic studies.

The correct evaluation of pharmacokinetic and biopharmaceutic data can only be achieved if accurate analytic data are obtained. The accuracy of analytic data depends on the criteria used to validate the method. Consequently, careful scrutiny of drug stability, assay sensitivity, selectivity, recovery, linearity, precision, and accuracy is necessary for the proper interpretation of data. The importance of method validation and its influence on pharmacokinetic and biopharmaceutic data evaluation and interpretation will be discussed.

Biopharmaceutics↗

PubMed2004

Biopharmaceutics of beta-cyclodextrin derivative-based formulations of acitretin in Sprague-Dawley rats.

Acitretin, an active metabolite of etretinate, is as effective as etretinate in the treatment of psoriasis. Recently, we developed some water-soluble formulations of acitretin with 2-hydroxypropyl-beta-cyclodextrin (HPBCD)/randomly substituted methyl-beta-cyclodextrin (RMBCD). In this study, the biopharmaceutic properties of these formulations were tested in Sprague-Dawley rats. After single intravenous dosing (2.5, 5, or 10 mg/kg) with the HPBCD-based formulation, the area under the plasma concentration-time curve of acitretin increased proportionally with the dose and its clearance remained unchanged within the tested dose range. We also found that the RMBCD-based formulation of acitretin improved its bioavailability and decreased the variations in various pharmacokinetic parameters. The improved biopharmaceutic properties of RMBCD-based acitretin might be attributed to its enhanced aqueous solubility. The elimination of acitretin through bile excretion was also studied. Our results indicated that the major fraction of acitretin (approximately 40%) was excreted in the bile as beta-glucuronide conjugate and only trace amounts were excreted as unconjugated acitretin (approximately 0.5%). This finding further confirmed the importance of conjugated metabolism and biliary excretion in the elimination of this drug.

Acitretin↗

PubMedDate not supplied

Pharmacoeconomics: where is the link with pharmacokinetics and biopharmaceutics?

Several, mainly macroeconomic factors are putting increasing pressure on health care budgets. These budget constrains lead to cost containment measures by all partners involved in health care. Pharmacotherapy, too, is facing an increasing involvement in health economics or outcomes research. This paper will first deal with some basic principles of pharmacoeconomics. The relationship with pharmacokinetics and biopharmaceutics has perhaps not yet been an issue as such, though it should be pointed out that they play a key role in the efficiency of drug use. Many of the basic R&D investments aimed at developing cost-effective medicines should be founded on adequate pharmacokinetics. Also a rational use of drugs in practice can be achieved by adequate drug monitoring, resulting in a gain in cost-effectiveness. Last, but not least, pharmacokinetics and biopharmaceutics can offer opportunities for the rational use of new or existing pharmaceutical products and for the maintenance of a sufficient market share. Some of these more technical aspects are discussed in the second part of this presentation.

Aged↗

PubMed2005

Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system.

The Biopharmaceutics Classification System (BCS) was developed to allow prediction of in vivo pharmacokinetic performance of drug products from measurements of permeability (determined as the extent of oral absorption) and solubility. Here, we suggest that a modified version of such a classification system may be useful in predicting overall drug disposition, including routes of drug elimination and the effects of efflux and absorptive transporters on oral drug absorption; when transporter-enzyme interplay will yield clinically significant effects (e.g., low bioavailability and drug-drug interactions); the direction, mechanism, and importance of food effects; and transporter effects on postabsorption systemic drug concentrations following oral and intravenous dosing. These predictions are supported by a series of studies from our laboratory during the past few years investigating the effect of transporter inhibition and induction on drug metabolism. We conclude by suggesting that a Biopharmaceutics Drug Disposition Classification System (BDDCS) using elimination criteria may expand the number of Class 1 drugs eligible for a waiver of in vivo bioequivalence studies and provide predictability of drug disposition profiles for Classes 2, 3, and 4 compounds.

Animals↗

PubMed2006

Biopharmaceutical drug discovery using novel protein scaffolds.

In recent years, biopharmaceutical drug products have become hugely successful. However, they are often complex molecules that are expensive to manufacture. Commercial needs for cost-effective therapies have therefore led to the development of novel protein scaffold technologies that are increasingly being used for biopharmaceutical drug discovery. Major new scaffolds include single-domain antibodies, small modular immunopharmaceuticals, tetranectins, AdNectins, A-domain proteins, lipocalins and ankyrin repeat proteins. These scaffolds offer low-cost alternatives to classical antibody therapeutic strategies and some have shown early clinical promise. Further progress in the field will permit the commercially successful development of sophisticated protein therapeutics against complex disease targets.

Biopharmaceutics↗

PubMed2004

Biopharmaceutical characterization of sotalol-containing oral immediate release drug products.

The objective of this study was replacing an in vivo bioequivalence study by generating suitable in vitro data in order to get generic marketing authorisation. Solubility and permeability of sotalol hydrochloride were determined thereby achieving classification of this compound according to the biopharmaceutical classification system. In addition comparative investigation of in vitro dissolution properties of different Sota-saar formulations and the reference product provided satisfying justification to waive in vivo bioavailability (BA)/bioequivalence (BE) studies. The investigations on solubility were performed considering the highest dose strength in aqueous media (250 ml) with pH conditions between pH 1.0 and 7.5. Permeability was studied using the human colorectal carcinoma cell line Caco-2. In vitro as well as in vivo data suggest high permeability of the drug compound through the intestinal membrane. Thus, evaluation of solubility and permeability allow sotalol hydrochloride to be classified as biopharmaceutics classification system class I drug. In vitro dissolution profiles demonstrate comparable rapid dissolution (more than 85% in 15 min) for test and reference products. Summarizing, relevant prerequisites are fulfilled to waive BA/BE studies.

Administration, Oral↗

PubMed2005

Manufacturing, regulatory and commercial challenges of biopharmaceuticals production: a Finnish perspective.

Biopharmaceuticals product development is a broad and multidisciplinary field. Science and technology are combined with new manufacturing, regulatory and commercial challenges. However, although there is ample literature on the molecular biology and biochemistry of products, the implementation of processes from test tube to commercial scale has not received similar attention. Consequently, the present study aims to highlight, from practical point of view, some of the key issues involved with manufacturing technologies of biopharmaceuticals at a commercial scale. Regulatory requirements and investments are also addressed based on the practical experiences of start-up and small companies. Finland is used as a case-example of such companies as this is a EU-member state with strong technological growth and rapidly increasing number of biotech companies.

Biopharmaceutics↗

PubMed2000

New biopharmaceuticals in the USA: trends in development and marketing approvals 1995-1999.

The Tufts Center for the Study of Drug Development has collected data on the clinical and approval phases of the 26 new biopharmaceuticals approved by the US Food and Drug Administration between 1980 and 1999. Here, the data for biopharmaceuticals approved between 1995 and 1999 are presented grouped by product category, review status, orphan-drug designation and therapeutic indication, and the mean phase lengths are compared. They are also compared with the data for approvals during the periods 1982-1989, 1990-1994 and 1996-1998.

Animals↗

PubMed2000

Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system.

The objectives were: (1) to develop a more rapid, reduced serum culture system for Caco-2 monolayers, relative to the traditional 21-day, 10% fetal bovine serum (FBS) system; and (2) to determine the biopharmaceutical drug classification of an oral therapeutic agent using this new system. Caco-2 cells were grown in the six well format on polycarbonate filters, in medium containing 2% iron supplemented calf serum (sCS) and a combination of growth factors and hormones. After 4 days in culture, permeabilities of three marker compounds (metoprolol, mannitol, and taurocholate) across monolayers were determined, and compared to permeabilities from the traditional 21-day, 10% FBS system, using cells at similar passage number. Cell morphology, degree of cell differentiation, and the presence of two efflux pumps were assessed. The 2% sCS model was also used to classify the permeability of an oral therapeutic agent as high or low. No difference in permeability was observed for metoprolol transport (P = 0.38) between the two culture methods, and the values obtained were independent of passage number of the cells. Mannitol permeability was about 2-fold higher from the 2% sCS system, as compared to the 10% FBS system. Taurocholate permeability was low indicating the 2% sCS culture at 4 days lacked this particular active transporter capability. Electron micrographs of cells grown in the 2% sCS system at 4 days revealed the presence of microvilli and tight junctions. P-glycoprotein and an efflux pump for furosemide were functionally present. The 2% sCS system indicated the oral therapeutic agent as highly permeable, which agreed with the 10% FBS system. This new system provides a rapid, accurate, and economical option for passive permeability determination, and appears to be applicable to the proposed Biopharmaceutics Classification System (BCS).

Adrenergic beta-Antagonists↗

PubMed2000

Biopharmaceutics and pharmacokinetics in drug research.

With the synergistic and multiplicative interactions of rational drug design, recombinant biotechnology, combinatorial chemistry and high-throughput screening, millions of compounds are being synthesized by chemists. However, development of these drug candidates has often been impeded, if not terminated, due to biopharmaceutic and/or pharmacokinetic constraints. This has resulted in delays in development time and escalation of cost in the drug research programmes. So, the present emphasis is to reduce development time and cost, which is analogous to added patent life besides the enormous reduction in human suffering. In this compilation the important biopharmaceutic and pharmacokinetic approaches are discussed, which will help in the development of safe and more efficacious drugs with reduced development time and cost.

Biopharmaceutics↗

PubMed2000

Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards.

In the last decade, the regulatory bioequivalence (BE) requirements of drug products have undergone major changes. The introduction of the biopharmaceutics drug classification system (BCS) into the guidelines of the Food and Drug Administration (FDA) is a major step forward to classify the biopharmaceutical properties of drugs and drug products. Based on mechanistic approaches to the drug absorption and dissolution processes, the BCS enables the regulatory bodies to simplify and improve the drug approval process. The knowledge of the BCS characteristics of a drug in a formulation can also be utilized by the formulation scientist to develop a more optimized dosage form based on fundamental mechanistic, rather than empirical, information. This report gives a brief overview of the BCS and its implications.

Biological Availability↗

PubMed2003

The state of biopharmaceutical manufacturing.

The manufacturing of protein-based biopharmaceuticals is done in bacterial or mammalian cell cultures. While bacterial cultures are inexpensive, dependable, and approved by regulatory authorities, many complex proteins cannot be manufactured this way. Complex proteins must be manufactured in mammalian cell cultures to produce active products. Mammalian cell culture capacity is limited and has slowed the delivery of necessary biopharmaceutical products to patients. The nature of the production capacity problem and future outlook are critically examined.

Biopharmaceutics↗

PubMed1997

Pharmacoeconomics: where is the link with pharmacokinetics and biopharmaceutics?

Several, mainly macroeconomic factors are putting increasing pressure on health care budgets. These budget constraints lead to cost containment measures by all partners involved in health care. Pharmacotherapy, too, is facing an increasing involvement in health economics or outcomes research. This paper will first deal with some basic principles of pharmacoeconomics. The relationship with pharmacokinetics and biopharmaceutics has perhaps not yet been an issue as such, though it should be pointed out that they play a key role in the efficiency of drug use. Many of the basic R&D investments aimed at developing cost-effective medicines should be founded on adequate pharmacokinetics. Also a rational use of drugs in practice can be achieved by adequate drug monitoring, resulting in a gain in cost-effectiveness. Last but not least, pharmacokinetics and biopharmaceutics can offer opportunities for the rational use of new or existing pharmaceutical products and for the maintenance of a sufficient market share. Some of these more technical aspects are discussed in the second part of this presentation.

Biopharmaceutics↗

PubMed2003

Quantitative biopharmaceutics classification system: the central role of dose/solubility ratio.

PURPOSE: To develop a quantitative biopharmaceutics drug classification system (QBCS) based on fundamental parameters controlling rate and extent of absorption. METHODS: A simple absorption model that considers transit flow, dissolution, and permeation processes stochastically was used to illustrate the primary importance of dose/solubility ratio and permeability on drug absorption. Simple mean time considerations for dissolution, uptake, and transit were used to identify relationships between the extent of absorption and a drug's dissolution and permeability characteristics. RESULTS: The QBCS developed relies on a (permeability, dose/ solubility ratio) plane with cutoff points 2 x 10(-6)-10(-5) cm/s for the permeability and 0.5-1 (unitless) for the dose/solubility ratio axes. Permeability estimates, P(app) are derived from Caco-2 studies, and a constant intestinal volume content of 250 ml is used to express the dose/solubility ratio as a dimensionless quantity, q. A physiologic range of 250-500 ml was used to account for variability in the intestinal volume. Drugs are classified into the four quadrants of the plane around the cutoff points according to their P(app), q values, establishing four drug categories. i.e., I (P(app) > 10(-5) cm/s, q < or = 0.5), II (P(app) > 10(-5) cm/s, q > 1), III (P(app) < 2 x 10(-6) cm/s. q < or = 0.5), and IV (P(app) < 2 x 10(-6) cm/s, q > 1). A region for borderline drugs (2 x 10(-6) < P(app) < 10(-5) cm/s, 0.5 < q < 1) was defined too. For category I, complete absorption is anticipated, whereas categories II and III exhibit dose/ solubility ratio-limited and permeability-limited absorption, respectively. For category IV, both permeability and dose/solubility ratio are controlling drug absorption. Semiquantitative predictions of the extent of absorption were pointed out on the basis of mean time considerations for dissolution, uptake, and transit in conjunction with drug's dose/solubility ratio and permeability characteristics. A set of 42 drugs were classified into the four categories, and the predictions of intestinal drug absorption were in accord with the experimental observations. CONCLUSIONS: The QBCS provides a basis for compound classification into four explicitly defined drug categories using the fundamental biopharmaceutical properties, permeability, and dose/solubility ratio. Semiquantitative predictions for the extent of absorption are essentially based on these drug properties, which either determine or are strongly related to the in vivo kinetics of drug dissolution and intestinal wall permeation.

Algorithms↗

PubMed2000

Preclinical assessments of european union marketing authorisation applications for immunomodulatory biopharmaceuticals.

A review of preclinical assessment reports on immunomodulatory biopharmaceuticals submitted to the European Agency for Evaluation of Medicinal Products from 1995 to the middle of 1999 was conducted. Questions regarding the rationale for the preclinical development programmes were often put to the applicants. Effects mediated via changes of the immune function, including risks of reproductive toxicity and tumorigenicity, were of particular concern. This review indicates the need to further develop methods for safety testing of immunomodulatory biopharmaceuticals.

Adjuvants, Immunologic↗

PubMed2005

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension.

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

Biological Availability↗

PubMed2003

The identification of factors linked to the potential acceptance of transgenic biopharmaceuticals: an exploratory study.

In this exploratory study, Rogers' diffusion of innovation theory was used to identify which factors are likely to contribute to the potential acceptance of transgenic biopharmaceuticals (TG-Bs). These products are not yet available to the general public. A scale was designed to assess three of five core attributes related to the potential adoption rate of innovations (Rogers 1995), as well as to measure potential acceptance characteristics for biotechnology products. These attributes were relative advantage, compatibility with existing values, and complexity. In addition, two other characteristics were included: knowledge (Gartrell and Gartrell 1979) and perceived risks (Bauer 1960). The survey was completed by 74 consumers (78% response rate) using convenience sampling. The research findings show that Rogers' three core attributes are supported, but that knowledge andperceived risks were excluded from the model. The model for transgenic biopharmaceuticals consists of: 1. Consumer-related benefits (positively correlated to potential adoption). 2. New types of animals (negatively correlated to potential 3. Perceived complexity (negatively correlated to potential adoption). All the scaled items developed for this study were highly significant, which indicates that they can be used successfully by other researchers working in this field. As TG-Bs are a discontinuous innovation, biotechnology companies may need to present the benefits of these products, as well as the ease of their use prior to their launch, in order to increase their potential acceptance by consumers.

Adult↗