Julio A. Luna

Mathematical modeling of drug delivery from torus-shaped single-layer devices.

A mathematical modeling of controlled release of drug from torus-shaped single-layer devices is presented. Analytical solutions based on the pseudo-steady state approximation are derived. The reliability and usefulness of the model are ascertained by comparison of the simulation results with matrix-type vaginal ring experimental release data reported in the literature. A good agreement between the model prediction and the experimental data is observed. An analysis of the effect of the variation in torus design parameters on the solute release is also presented. The model is applicable only to torus-shaped single-layer systems wherein the initial load of drug is higher than its solubility in the polymer.

Recent Advances in Chitosan Films for Controlled Release of Drugs

Chitosan is a versatile carrier for biologically active agent from a small molecule such as an antibiotic to macromolecules such as proteins and nucleic acids. In addition, drug delivery devices based on chitosan can be available in a variety of morphologies including films, fibers, nanoparticles and microspheres. Otherwise the inherent advantages of this polymer such as biocompatibility, tissue adhesions and hydrophilic nature, chitosan can be modified to accomplish a specific purpose, for example improves release kinetics. In this review, recent patents of chitosan-based film systems for drug delivery are presented and discussed. This review include matrix type systems, membrane coated systems and film forming solution. For each one of these systems, several examples of manufacture processes, bioactive agents to be delivered and specifics applications are considered. This work highlights the use of chitosan in the film technology for drug delivery, presenting examples of chitosan used in an unmodified state and examples of modifications of the polymer backbone.

Modeling of dispersed-drug delivery from planar polymeric systems: optimizing analytical solutions.

Analytical solutions for the case of controlled dispersed-drug release from planar non-erodible polymeric matrices, based on Refined Integral Method, are presented. A new adjusting equation is used for the dissolved drug concentration profile in the depletion zone. The set of equations match the available exact solution. In order to illustrate the usefulness of this model, comparisons with experimental profiles reported in the literature are presented. The obtained results show that the model can be employed in a broad range of applicability.

In Situ-Formed Microparticles of PLGA from O/W Emulsions Stabilized with PVA: Encapsulation and Controlled Release of Progesterone

In situ-formed microspheres are an alternative to expensive and complex manufactured preformed systems for the controlled release of drugs. The aim of this study was to evaluate the potential of stable O/W emulsions to entrap progesterone after in vitro precipitation of poly(d,l-lactide-co-glycolide) (PLGA) microparticles. This was achieved by a solvent selection based on their miscibility and capability to solubilize the drug and PLGA. Stability assays, size distribution studies, and progesterone encapsulation efficiency evaluation were carried out for the candidate formulations. After selection of the most suitable formulations, in vitro-controlled release test of progesterone were done. Results demonstrate that emulsions based on triacetin and polyvinyl alcohol (PVA) aqueous solutions were useful solvent systems to obtain microspheres capable to deliver the hormone in a controlled release manner. In addition, for the first time, for these authors, PVA was successfully implemented into a continuous phase to increase the stability of in situ-formed O/W formulations.

Mathematical modeling of drug delivery from one-layer and two-layer torus-shaped devices with external mass transfer resistance.

A mathematical modeling of controlled release of drug from one-layer and two-layer torus-shaped devices with external mass transfer resistance is presented. Analytical solutions based on the pseudo-steady state approximation are derived. The validity of the equations is established in two stages. In the first stage, the validity of the models derived for more complex systems is determined by comparison with profiles predicted by the simplest model, in asymptotic cases. In the second stage, the reliability and usefulness of the models are ascertained by comparison of the simulation results with vaginal rings experimental release data reported in the literature. In order to measures quantitatively the fit of the theoretical models to the experimental data, the pair-wise procedure is used. A good agreement between the prediction of the models and the experimental data is observed. The models are applicable only to torus-shaped systems in where the initial load of drug is higher than its solubility in the polymer.

Development of an injection molded ethylene-vinyl acetate copolymer (EVA) intravaginal insert for the delivery of progesterone to cattle.

The purpose of this study was to develop a new injection-molded intravaginal insert manufactured from ethylene-vinyl acetate containing progesterone for a 7-day insertion period in cattle. The manufacturing process resulted in a reduction in the residual drug compared to the silicone insert available while still maintaining biological performance.

Application of the Refined Integral Method in the mathematical modeling of drug delivery from one-layer torus-shaped devices

A mathematical modeling of controlled release of drug from one-layer torus-shaped devices is presented. Analytical solutions based on Refined Integral Method (RIM) are derived. The validity and utility of the model are ascertained by comparison of the simulation results with matrix-type vaginal rings experimental release data reported in the literature. For the comparisons, the pair-wise procedure is used to measure quantitatively the fit of the theoretical predictions to the experimental data. A good agreement between the model prediction and the experimental data is observed. A comparison with a previously reported model is also presented. More accurate results are achieved for small A/C(s) ratios.

Solving design equations for a hollow fiber bioreactor with arbitrary kinetics

Abstract An approach for solving the hollow fiber bioreactor design equations is presented. The original set of differential mass balance equations is cast into an equivalent system of integral equations by generating the appropriate Green’s functions. Mathematical features common to all hollow fiber bioreactors (HFBRs) operating with laminar flow are imbedded in the corresponding Green’s functions on the lumen side, and thus separated from specific aspects arising from mass transport through the permeable wall. On the spongy matrix side, the appropriate Green’s functions are expressed in terms of the mass transfer properties without involving any chemical kinetic parameters; this avoids repetitive computational effort when treating different reaction kinetics. The derived integral equations are numerically solved on an appropriately transformed coordinate system. The numerical method is well suited for problems where steep gradients of concentration cause an inaccurate numerical integration and low rates of convergence if the equations are solved with a uniform rectangular grid on the original coordinate system. The effectiveness of the proposed approach for the simulation of HFBRs with power-law, Michaelis–Menten and zero-order kinetics is demonstrated. The method is readily extendible to treat problems with chemical kinetics described by any arbitrary functional form.

In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres and controlled release of progesterone

Abstract One possibility to obtain a higher dose of drug in a lower formulation volume can be by using of saturated quantity of drug in one of the phases of an emulsion. These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer is added to the organic phase of suspoemulsions, these formulations can be used to entrap the drug inside microspheres after in situ precipitation of the polymer–drug–excipients mix. In this work, performance and stability of progesterone suspensions in triacetin as organic phase of suspoemulsions were evaluated. These formulations were compared with O/W emulsions. Mathematical models were used to study in vitro release profiles. The results confirmed that S/O/W systems could be an attractive alternative to O/W formulations for the entrapment of progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based models fit the in vitro release of progesterone from in situ-formed microspheres. For longer release periods, a time-dependent diffusion coefficient was successfully estimated.

Effect of particle size, polydispersity and polymer degradation on progesterone release from PLGA microparticles: Experimental and mathematical modeling

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results.