Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems.
ABSTRACT This article aims to provide a comprehensive review of existing mathematical models and simulations of drug release from polymeric microspheres and of drug transport in adjacent tissues. In drug delivery systems, mathematical modeling plays an important role in elucidating the important drug release mechanisms, thus facilitating the development of new pharmaceutical products by a systematic, rather than trial-and-error, approach. The mathematical models correspond to the known release mechanisms, which are classified as diffusion-, swelling-, and erosion-controlled systems. Various practical applications of these models which explain experimental data are illustrated. The effect of gamma-irradiation sterilization on drug release mechanism from erosion-controlled systems will be discussed. The application of existing models to nanoscale drug delivery systems specifically for hydrophobic and hydrophilic molecules is evaluated. The current development of drug transport modeling in tissues utilizing computational fluid dynamics (CFD) will also be described.
SourceAvailable from: Joachim SC Loo[Show abstract] [Hide abstract]
ABSTRACT: Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.PLoS ONE 12/2014; 9(12):e114284. DOI:10.1371/journal.pone.0114284 · 3.53 Impact Factor
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ABSTRACT: Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery.International Journal of Nanomedicine 01/2014; 9:4723-35. DOI:10.2147/IJN.S65262 · 4.20 Impact Factor
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ABSTRACT: This study aimed to develop drug delivery system of doxycycline-loaded polycaprolactone (PCL) microspheres. The investigated microsphere formulation can be considered for local application in bone infections and degenerative joint diseases, which generally require long-term treatments via systemic drugs. PCL-14 kDa and 65 kDa were used in microsphere preparation. Before release, the microspheres were characterized by scanning electron microscopy, differential scanning calorimetry, and X-ray photoelectron spectroscopy. The mean particle size of microspheres was in the range of 74–122 µm and their drug loadings ranged between 10 and 30%. In vitro release profiles were described using the Higuchi and the Korsmeyer–Peppas equations. Diffusion model was applied to experimental data for estimating diffusion coefficients of microspheres; calculated as between 4.5 × 10−10 and 9.5 × 10−10 cm2/s. Although long-term release from microspheres of PCL-14 kDa obeyed diffusion model, PCL-65 kDa microspheres showed this tendency only for some period. Modeling studies showed that the drug release mechanism was mainly dependent on loading and molecular weight differences. Release behavior of PCL-65 kDa microspheres, however, might be better represented by derivation of a different equation to model for the total release period. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 000: 000–000, 2014Journal of Applied Polymer Science 12/2014; 132(14). DOI:10.1002/app.41768 · 1.40 Impact Factor