Johnson Kevin Charles

Bio: Johnson Kevin Charles is an academic researcher from Pfizer. The author has contributed to research in topics: Particle size & Tartrate. The author has an hindex of 5, co-authored 7 publications receiving 691 citations.

Guidance in the setting of drug particle size specifications to minimize variability in absorption.

Abstract: Purpose To provide guidance in setting particle size specifications for poorly soluble drugs to minimize variability in absorption Methods A previously reported computer method was used to simulate the percent of dose absorbed as a function of solubility, absorption rate constant, dose, and particle size Results The simulated percent of dose absorbed was tabulated over a realistic range of solubilities, absorption rate constants, and doses using drug particle sizes that might be typically found in a dosage form Conclusions The greatest effect of particle size on absorption was simulated for low dose- low solubility drugs In general, the sensitivity of absorption to particle size decreased with increasing dose or solubility At a solubility of 1 mg/mL, particle size had practically no effect on the percent of dose absorbed over the range of doses simulated (1–250 mg)

Dissolution modeling: factors affecting the dissolution rates of polydisperse powders

Abstract: The dissolution rates of two lots of hydrocortisone (fine and coarse) were simulated using a computer program based on a Noyes–Whitney-type equation. Derivations of the equation were made to compare the accuracy of simulations using spherical and cylindrical particle geometry, with and without a time-dependent diffusion layer thickness. To approximate better the shape of the hydrocortisone particles, a shape factor was used to relate cylindrical length to radius. The most accurate simulations were obtained by assuming cylindrical geometry with and without a time-dependent diffusion layer thickness for the fine and coarse hydrocortisone, respectively. The program was also modified to simulate initial particle size distributions based on the log normal probability density function.

Inclusion complexes of aryl-heterocyclic salts

Abstract: Compositions of matter comprising a pharmaceutically acceptable salt of an aryl-heterocyclic compound, such as ziprasidone, in a cyclodextrin. Preferred cyclodextrins are SBECD and HPBCD. The composition can comprise a dry mixture, a dry inclusion complex or an aqueous solution. The salt/cyclodextrin inclusion complex preferably provides an amount of ziprasidone of at least 2.5 mgA/ml when the complex is dissolved in water at 40 % w/v. A variety of ziprasidone salts are preferred, including the mesylate, esylate, besylate, tartrate, napsylate, and tosylate.

A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability

Abstract: A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes. This classification scheme provides a basis for establishing in vitro-in vivo correlations and for estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance.

Strategies to Address Low Drug Solubility in Discovery and Development

Abstract: Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Bioavailability of nanoparticles in nutrient and nutraceutical delivery

Abstract: The field of nanoparticle delivery systems for nutrients and nutraceuticals with poor water solubility has been expanding, almost exponentially, over the last five years, and some of these technologies are now in the process of being incorporated in food products. The market projections for these technologies suggest a multifold increase in their commercial potential over the next five years. The interest in the pharmaceutical and food-related applications of these technologies has sparked tremendous developments in mechanical (top-down) and chemical (bottom-up) processes to obtain such nanoparticle systems. Mechanical approaches are capable of producing nanoparticles, typically in the 100–1000 nm range, whereas chemical methods tend to produce 10–100 nm particles. Despite these technological developments, there is a lack of information regarding the basis of design for such nanoparticle systems. Fundamental thermodynamic and mass transfer equations reveal that, in order to generate a broad spectrum delivery system, nanoparticles with 100 nm diameter (or less) should be produced. However, experimental data reveal that, in some cases, even nanoparticles in the 100–1000 nm range are capable of producing substantial improvement in the bioavailability of the active ingredients. In most cases, this improvement in bioavailability seems to be linked to the direct uptake of the nanoparticle. Furthermore, direct nanoparticle uptake is controlled by the size and surface chemistry of the nanoparticle system. The use of this direct nanoparticle uptake, in particular for soluble but poorly absorbed ingredients, is one of the areas that needs to be explored in the future, as well as the potential side effects of these nanoparticle carriers.