Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Two Strategies to Enhance Ungual Drug Permeation from UV-cured Films: Incomplete Polymerisation to Increase Drug Release and Incorporation of Chemical Enhancers

UV-curable gels, which polymerise into long-lasting films upon exposure to UVA, have been identified as potential topical drug carriers for the treatment of nail diseases. Limitations of such films include incomplete drug release and low ungual drug permeation. The aim of the work herein was therefore to investigate two strategies, namely: (1) increasing drug release from the film, and (2) increasing nailplate permeability, with the ultimate goal of enhancing ungual drug permeation. To increase drug release via Strategy 1, a UV-LED lamp (whose emitted light was suboptimal for gel polymerisation) was used, and it was hypothesised that such a lamp would result in films that are less polymerised/cross-linked and where the drugs are less ‘trapped’. Indeed, the suboptimal lamp influenced polymerisation, such that the films were thinner, had lower glass transition temperatures and enabled a slightly greater (by 15%) drug release of one of the two drugs tested. However, the greater drug release had only a modest impact on ungual drug permeation. To evaluate Strategy 2, i.e. increase nailplate permeability, chemical ungual enhancers, 2-mercaptoethanol (ME), 2-methyl pyrrolidone (NMP), PEG 200 and water were incorporated within the UV-cured films. These chemicals caused increased ungual drug permeation, with ME showing the greatest (by 140%), and water showing the least (by 20%) increase in the amount of drug permeated by day 30. Surprisingly, these chemicals also caused increased drug release from the films, with ME once again having the greatest effect (by 51%) and water the least effect (by 12%). It seems that these chemicals were increasing ungual drug permeation via their influence on drug release (i.e. via their impact on the film) as well as via their influence on the nail itself. We conclude that, of the two strategies tested, the second strategy proved to be more successful at enhancing ungual drug permeation.Peer reviewe

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

Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

Fabrication and Characterization of Electrospun Drug-eluting Nanofibers from Polycaprolactone/Chitosan Blends

Electrospinning has emerged as a widely accepted technique with ability to produce nanofibers that can be employed in many biomedical applications. In particular, drug-eluting nanofibers have become very popular in controlled release of small molecule drugs. In this study, nanofibers from blends of polylactocaprone (PCL) and chitosan (CHI) were electrospun with the ability to load a model drug, acetylsalicylic acid (ASA), at 10 wt%. PCL/CHI fibers exhibited smooth surface morphology at polymer compositions ranging from 100/0 to 40/60 with or without the incorporation of ASA. Mechanical properties suggested a brittle failure mechanism for fibers loaded with drug. In vitro drug release study displayed a controlled release profile of ASA up to 48 h. Our study aims to explore the drug-polymer interactions and their effects on fiber structure, mechanical properties and drug release profile.Cockrell School of Engineerin

Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model. © 2011 by Tabriz University of Medical Sciences

Adriamycin loading and release characteristics of albumin-heparin conjugate microspheres

Biodegradable ion-exchange microspheres, prepared from a prefabricated conjugate of albumin and heparin were investigated as carriers for adriamycin. The ion-exchange microspheres could be loaded with adriamycin giving payloads up to 33% w/w, depending on the heparin content of the conjugate. In vitro adriamycin release depended on the ionic strength of the release medium. In ion containing media, for instance saline, 90% of the drug was released within 45 min, whereas in non-ionic media, such as distilled water, only 30% was released. Drug release profiles could be modelled by combining ion-exchange kinetics and diffusion controlled drug release models