The Effect of Configuration to Interaction Energy Between The Segments of Chitosan and Ascorbic Acid Molecule: Theoretical Study of Drug Release Control

Polymer systems plays an important role in drug delivery, which can control the time release of the drug, reduce the rate of degradation of the drug, and can reduce the toxic properties of the drug. Chitosan is a polymer of N-acetyl glucosamine that is biocompatible, biodegradable, and have active groups that can be used as a drug carrier matrix to control the release rate of the drug in the human body. The related research has been conducted experimentally by applying chitosan as a matrix to control the release rate of ascorbic acid by in vitro in an aqueous medium. So that, this study aimed to describe the interactions that occur between segments of chitosan and ascorbic acid theoretically using ab initio computational methods. Software used is Gaussian03, while the level of theory and basis set calculations determined is HF-SCF / 6-31G (d, p). The results for the nine configuration interaction calculations indicate hydrogen bonds between ascorbic acid molecules and chitosan segment. The interaction energy obtained is different for each configuration. It can be used as a basis for explaining the gradual release of ascorbic acid molecule from chitosan matrix. Ascorbic acid molecules that bound to the matrix of chitosan with lower energy will be easier to release on the medium that used

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

Biodegradable hollow fibres for the controlled release of drugs

Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug release was compared with the release in vitro using different release media. Fibres, disinfected with alcohol showed a zero-order release, both in vitro and in vivo, for over 6 months. Fibres, either γ-sterilized or disinfected with alcohol were harvested at time intervals ranging from 1 d to 6 months after implantation. Molecular weights of PLLA, tensile strengths, and remaining amounts of drug were determined as a function of time.\ud \ud The tissue reaction can be described as a very moderate foreign body reaction with the initial presence of macrophages, which are gradually replaced by fibroblasts which form a collagen capsule. Molecular weight determinations of PLLA showed a decrease from an initial Mw of 1.59x10 5 to 5.5 × 10 4 in 4 months (after alcohol sterilization). A gradual decrease in fibre strength with time was observed which did not significantly impair the release rate of levonorgestrel

Mathematical Modelling of Variable Porosity Coatings for Dual Drug Delivery

In this paper we describe a theoretical mathematical model of dual drug delivery from a durable polymer coated medical device. We demonstrate how the release rate of each drug may in principle be controlled by altering the initial loading configuration of the two drugs. By varying the underlying microstructure of polymer coating, further control may be obtained, providing the opportunity to tailor the release profile of each drug for the given application

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

Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds

A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

FORMULATION AND EVALUATION OF FLUVOXAMINE CONTROLLED RELEASE TABLETS

A controlled drug delivery system is usually designed to deliver the drug at the particular rate. The performance of a drug presented as a controlled-release system depends upon its release from the formulation. Movement within the body during its passage to the site of action. The former depends upon the fabrication of the formulation and the physicochemical properties of the drug while the latter element is dependent upon pharmacokinetics of drug. In comparison to conventional dosage form where the rate-limiting step in drug availability is usually absorption through the biomembrane, the rate-determining step in the availability of a drug from controlled delivery system is the rate of release of drug from the dosage form which is much smaller than the intrinsic absorption rate for the drug. The objective of the development programme was to formulate a robust, stable formulation of Fluvoxamine controlled release tablets 100mg comparable to the reference product Fluvoxin CR 100mg(Luvox) in terms of in-vitro dissolution profile. Matrix tablets were compressed without any problem and do not require any change in ratio of excipients in formulation. Results of the present study demonstrated that hydrophilic polymers could be successfully employed for formulating controlled-release matrix tablet of fluvoxamine. Formulations containing polymer percentage 15% controlled the drug release for 12 h. The combination of drug Fluvoxamine, lubricant [SSF] and glidant[Aerosil] was showed high drug release profile. Wet granulation method was found to be better choice to extend the drug release for 12 h. Film coating of tablet is beneficial for protecting the drug

Bioactive SrO-SiO2 glass with well-ordered mesopores: Characterization, physiochemistry and biological properties

For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO2 in an effort to develop a bioactive mesoporous SrO–SiO2 (Sr–Si) glass with the capacity to deliver Sr2+ ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr2+ on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr–Si glass were investigated. The prepared mesoporous Sr–Si glass was found to have an excellent release profile of bioactive Sr2+ ions and dexamethasone, and the incorporation of Sr2+ improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr–Si glass had no cytotoxic effects and its release of Sr2+ and SiO44− ions enhanced alkaline phosphatase activity – a marker of osteogenic cell differentiation – in human bone mesenchymal stem cells. Mesoporous Sr–Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr2+ into mesoporous SiO2 glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications. Keywords: Mesoporous Sr–Si glass; Drug delivery; Bioactivity; Bone repair; Scaffold