Controlled Drug Release Asymptotics

The solution of Higushi's model for controlled release of drugs is examined when the solubility of the drug in the polymer matrix is a prescribed function of time. A time-dependent solubility results either from an external control or from a change in pH due to the activation of pH immobilized enzymes. The model is described as a one-phase moving boundary problem which cannot be solved exactly. We consider two limits of our problem. The first limit considers a solubility much smaller than the initial loading of the drug. This limit leads to a pseudo-steady-state approximation of the diffusion equation and has been widely used when the solubility is constant. The second limit considers a solubility close to the initial loading of the drug. It requires a boundary layer analysis and has never been explored before. We obtain simple analytical expressions for the release rate which exhibits the effect of the time-dependent solubility

Controlled release device Patent

Controlled release device for use in launching rockets or missile

Melt-extruded polyethylene oxide (PEO) rods as drug delivery vehicles: Formulation, performance as controlled release devices and the influence of co-extruded excipients on drug release profiles

The utility of controlled release medication formulations lies in their ability to keep drugs at steady levels in the blood plasma of recipients and within the termini of the maximum and minimum effective therapeutic levels. This avoids the “ups” and “downs” of medication levels within the body which would have been the result had conventional immediate release tablets been administered instead. In the veterinary field, controlled release medications are essential¹ because of the logistical difficulties of administering drugs on a regular (e.g., daily) basis to animals. The chief advantages of controlled release veterinary medications lie in the ease with which they can be administered; decrease in stress for animals, owing to less need for rounding up and frequent dosing; and, most importantly for farmers, the reduced cost of treatment relative to that for a multiple dosage regime

Controlled release nanoparticulate matter delivery system

A controlled release nanoparticulate matter delivery system includes a plurality of thermoresponsive modules containing a respective nanoparticulate matter. Each thermoresponsive module is selectively operable in at least one of a heating mode that releases the nanoparticulate matter and a cooling mode that inhibits release of the nanoparticulate matter. A control module is in electrical communication with the plurality of thermoresponsive modules. The control module is configured to determine a temperature of each thermoresponsive module and to select the at least one heating mode and cooling mode based on the temperature. The heating and cooling mode may be selected in response to a desired dosing profile and/or a biometric condition.Board of Regents, University of Texas Syste

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Controlled-release fertilizers: advances and challenges

Controlled- release fertilizers (CRFs) offer an excellent option to improve nutrients uptake by plants and reduce the environmental hazards due to excess release of chemicals. Polymer-coated fertilizers, compared to the other types of CRF, are by far the most intensively researched topic because of their great characteristics. Polymer-coated fertilizers, which are less sensitive to the soil and environmental factors, offer superior control over nutrients release for plants uptake. In recent years, the art has mainly focused on the design of biodegradable polymer-based coating for fertilizers considering the effective control on nutrient release. This review covers the basic information about CRFs with an emphasis on the development of polymer-coated fertilizers. Topics that are discussed herewith include materials and methods utilized for coated fertilizer, particularly polymer-coated fertilizers, manufacturing and related issues. The large market potential for fertilizer using necessitates more studies for development and commercial production of polymer-coated fertilizers

Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds

open access articleTissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)- N0-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen

High-Affinity Phosphate-Binding Protein (PBP) For Phosphorous Recovery: Proof of Concept Using Recombinant \u3cem\u3eEscherichia coli\u3c/em\u3e

Phosphorus (P) is a critical, non-renewable nutrient; yet excess discharges can lead to eutrophication and deterioration of water quality. Thus, P removal from water must be coupled with P recovery to achieve sustainable P management. P-specific proteins provide a novel, promising approach to recover P from water. Bacterial phosphate-binding proteins (PBPs) are able to effectively remove phosphate, achieving extremely low levels in water (i.e. 0.015 mg-P L−1). A prerequisite of using PBP for P recovery, however, is not only removal, but also controlled P release, which has not yet been reported. Phosphate release using recombinant PBP-expressing Escherichia coli was explored in this study. Escherichia coli was genetically modified to overexpress PBP in the periplasmic space. The impacts of ionic strength, temperature and pH on phosphate release were assessed. PBP-expressed E. coli demonstrated consistently superior ability to adsorb more phosphate from liquid and release more phosphate under controlled conditions relative to negative controls (unexpressed PBP E. coli and E. coli K12). Lower pH (3.8), higher temperature (35ºC) and higher ionic strength (100 mM KCl) facilitated increased phosphate release, providing a maximum of 2.1% P recovery within 3 h. This study provides proof of concept of the feasibility of using PBP to recover P

Trends and uptake of new formulations of controlled-release oxycodone in Canada

Purpose: This study investigated the impact of changing availability of tamper‐deterrent and non‐tamper‐deterrent oxycodone on prescribing patterns of controlled‐release oxycodone across Canada. Methods: We conducted a population‐based, serial cross‐sectional study of controlled‐release oxycodone dispensing from community pharmacies across Canada between October 2007 and April 2016. We calculated rates of dispensing (tablets per 100 population) and reported the relative market share of generic non‐tamper‐deterrent controlled‐release oxycodone. All analyses were reported nationally and stratified by province. Results: After the introduction of a tamper‐deterrent formulation, the national rate of controlled‐release oxycodone dispensing fell by 44.6% (from 26.4 to 14.6 tablets per 100 population from February 2012 to April 2016). Between December 2012 and July 2013, there was moderate uptake of generic non‐tamper‐deterrent controlled‐release oxycodone (968 452 tablets; 16.0% in July 2013), which appeared to have little impact on the overall rate of controlled‐release oxycodone dispensing in Canada. However, the uptake of generic non‐tamper‐deterrent oxycodone varied considerably by province. By April 2016, 55.0% of all controlled‐release oxycodone tablets dispensed in Quebec were for the generic formulation. […

Remotely triggered scaffolds for controlled release of pharmaceuticals

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold