Controlled Drug Release Kinetics Research Articles

Mathematical Modeling for Pharmaco-Kinetic and -Dynamic Predictions from Controlled Drug Release NanoSystems: A Comparative Parametric Study.

Predicting pharmacokinetics, based on the theory of dynamic systems, for an administered drug (whether intravenously, orally, intramuscularly, etc.), is an industrial and clinical challenge. Often, mathematical modeling of pharmacokinetics is preformed using only a measured concentration time profile of a drug administered in plasma and/or in blood. Yet, in dynamic systems, mathematical modeling (linear) uses both a mathematically described drug administration and a mathematically described body response to the administered drug. In the present work, we compare several mathematical models well known in the literature for simulating controlled drug release kinetics using available experimental data sets obtained in real systems with different drugs and nanosized carriers. We employed the χ2 minimization method and concluded that the Korsmeyer–Peppas model (or power-law model) provides the best fit, in all cases (the minimum value of χ2 per degree of freedom; χmin2/d.o.f. = 1.4183, with 2 free parameters or m = 2). Hence, (i) better understanding of the exact mass transport mechanisms involved in drugs release and (ii) quantitative prediction of drugs release can be computed and simulated. We anticipate that this work will help devise optimal pharmacokinetic and dynamic release systems, with measured variable properties, at nanoscale, characterized to target specific diseases and conditions.

Gradiently degraded electrospun polyester scaffolds with cytostatic for urothelial carcinoma therapy.

Kidney-sparing surgery is the preferred treatment strategy for low-risk upper tract urothelial carcinoma (UTUC). However, after this procedure, prevention of the carcinoma recurrence in the ureter and supporting the ureter with a ureteral stent are necessary. Biodegradable drug-loaded ureteral scaffolds are able to maintain their long-term effective drug concentrations in the lesion sites without the defects of traditional ureteral stents, which may address both issues simultaneously. The purpose of this study was to reveal the possibility of the controlled delivery of epirubicin (EPI) via gradiently degraded electrospun poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffolds to evaluate their antitumor activity against UTUC. The degradable PCL/PLGA scaffolds containing 15.0 and 25.0 wt% PCL and loading of 0, 5.0, and 10.0 wt% EPI were successfully fabricated via electrospinning. In addition, the PCL/PLGA scaffolds showed sustained and controlled degradation and drug release kinetics, that is, their degradation and drug release rates slowed with an increase in the ratio of PCL. The EPI-loaded PCL/PLGA scaffolds showed excellent antitumor activities both in vitro and in vivo without apparent systemic toxicity. Overall, the gradiently-degraded EPI-loaded electrospun polyester scaffolds are potential ureteral stent tubes for the local inhibition of the recurrence of UTUC, where the continued release of EPI can prevent the subsequent proliferation of residual tumor cells, and the gradient degradation is consistent with the repair of the ureter.

Amphiphilic Drug Conjugates as Nanomedicines for Combined Cancer Therapy.

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.

Multifunctional electrospun nanofibers for wound application – Novel insights into the control of drug release and antimicrobial activity

Therapeutic management of skin wounds is still faced with major challenges associated with chronicity and bacterial infection. Consequently, there is a high clinical need for effective therapeutic approaches addressing these aspects. In this context, electrospun fibers emerged as beneficial carrier systems for local and controlled delivery of wound healing agents, additionally providing a protective barrier against bacterial invasion. However, depending on the material, such fibers were also shown to provide a potential substrate for bacterial colonization and growth. Thus, profound understanding of fiber characteristics and the respective interactions of fibers with biological systems, cells as well as bacteria, is of major importance.To address these issues, we designed drug-loaded hybrid fibers consisting of polycaprolactone (PCL) and chitosan. Pure PCL fibers provided suitable drug release kinetics for wound healing, but were colonized by Pseudomonas bacteria which were used as model pathogens. The addition of chitosan to the fiber matrix reduced the number of adherent bacteria by tenfold compared to pure PCL fibers and did not show any adverse effects to human skin cells. Further, chitosan incorporation significantly improved fiber hydrophilicity, identified as one of the key regulators of optimized cell-fiber interactions. We successfully encapsulated dexpanthenol as an established wound healing active into these hybrid fibers and solvent polarity was found to be a key factor for controlling drug release kinetics from the fibers. For the final formulation, controlled drug release over seven days with a burst release of 11.54% within 3 h could be achieved and the wound healing effect of the fiber mats could successfully be demonstrated in a cell-based wound healing assay as a proof-of-concept. Such multifunctional fibers simultaneously deliver actives and prevent bacterial growth, and consequently show a high potential for future wound therapy.

MPEG-g-CS-Modified PLGA Nanoparticle Carrier for the Codelivery of Paclitaxel and Epirubicin for Breast Cancer Synergistic Therapy.

The aim of this study was to investigate a novel double-layer core-shell structure nanoparticle (NP) delivery system, comprising a nanoscale self-assembly mPEG-g-CS envelope coating on a nuclear PLGA NPs. We then constructed the core-shell NPs for paclitaxel (PTX) loading in the outer envelope to target tumor neovasculature and epirubicin (EPI) loading in the core to antitumor cells. We characterized the NPs for physical/chemical properties, controlled drug release kinetics, and finally evaluated in vitro and in vivo antitumor activities. It could be seen that these three blank NPs (core-shell NPs, PLGA NPs, and mPEG-g-CS NPs) had no significant influence on the cell viability of human breast adenocarcinoma cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC) in a NPs concentration range of 0.5-1000 μg/mL for 24 and 48 h, thus it can be inferred that the NPs constructed by mPEG-g-CS and PLGA polymers have good biocompatibility for further application. The confocal images and flow cytometry results showed that the core-shell NPs were efficiently internalized by these cells. After intravenous injection to nude mice bearing MCF-7 breast tumor, core-shell NPs achieved enhanced antitumor and antiangiogenic effects, prolonged retention, increased distribution, and significantly reduced microvessel density (MVD) in tumor tissues compared to both PLGA NPs and mPEG-g-CS NPs. In conclusion, this novel NPs system represent a new way of combining traditional combination chemotherapy and antiangiogenesis therapy for controlled drug delivery applications, and appeared to be a promising combination therapy to treat breast cancer.

In Situ-Based Gels for Nose to Brain Delivery for the Treatment of Neurological Diseases.

In situ-based gel drug delivery systems that can bypass the blood-brain barrier, deliver the therapeutics to the desired site, reduce peripheral toxicity and control drug release kinetics have been developed. Some of the therapeutics used to treat neurological diseases suffer from poor bioavailability. Preclinical reports from several researchers have proven that the delivery of drugs to the brain via the nose-to-brain route using in situ gels holds great promise. However, safety issues on the toxicity of the nasal mucosa, transportation of the drugs to specific brain regions and determination of the required dose are factors that must be considered when designing these gels. This review will be focused on in situ-based gels that are used for the delivery of therapeutics via the nose-to-brain route, preclinical reports and challenges.

Macro-scale model study of a tunable drug dispensation mechanism for controlled drug delivery in potential wound-healing applications.

Auxetic materials tend to exhibit stretching in the direction of the applied load as well as in the perpendicular direction. This may be an inherent property of the material, or it might be a particular structural characteristic that confers it with auxetic properties. In this study, the auxetic properties of a rotating squares auxetic design were utilized in tandem with a stretching mechanism to manufacture a device that offers the advantages of adjustable pore size and hence tunable drug delivery characteristics. An auxetic polyurethane film was fabricated through the polymer casting technique. An acrylonitrile-butadiene-styrene (ABS) plastic mold for polymer casting was made through additive manufacturing. Stereolithography was used for fabrication of the mechanism that controlled pore size of the polymeric auxetic film. A laminate arrangement of the film and the mechanism was devised, through which movement of the mechanism controlled stretching of the auxetic film underneath. Results were analyzed through image processing. It was observed that a 2-dimensional increase (in length and width) of the auxetic film took place that corresponded to an increase in pore size of the film. Several mathematical correlations were drawn up. It may be concluded that the first factor controlling drug release kinetics is the pore size of the film. This study explored a prototype mechanism that has the potential for being used in devices for controlled drug delivery or in smart bandage systems that may enhance wound healing in chronic wound treatment.

Abstract 12072: Damage to Coating Polymer Can Cause Serious Complications After Drug-Eluting Stent Implantation: A Pathological Study in Human Coronary Arteries

Introduction: Polymer coating is indispensable to optimize controlled drug release kinetics following drug-eluting stent (DES) implantation. However, how it can be damaged during the stenting procedure and the subsequent clinico-pathological events are not well studied. Hypothesis: We histopathologically assessed the hypothesis that damage to polymer coating can hinder DES efficacy. Methods: The study sample comprised 32 DES-implanted lesions obtained by autopsy from 2.5 to 49 months after stenting: 27 with durable polymers (Cypher, 12; Taxus, 6; Endeavor, 4; and Xience, 5) and 5 with biodegradable polymers coated only on the abluminal surface (Nobori, 3 and Ultimaster, 2). Tortuous lesions accounted for 60% and calcified lesions for 88%. We examined microscopically at least six slices from each lesion. Results: Polymer cracking or delamination was observed in about 6% of Cypher struts and 4% of Taxus struts. In two Cypher-implanted lesions with stent thrombosis occurring beyond one year after stent implantation, significant detachment of polymer fragments phagocytosed by giant cells was observed, and their arterial walls were aneurysmally dilated with extensive inflammatory infiltration of the intima, media, and adventitia, predominantly consisting of T cells, eosinophils, and considerable giant cells. In Xience-implanted lesions, polymer damage was little. In contrast, in most Endeavor-implanted lesions, large spallings of the polymer were found, and numerous phagocytosed polymer remnants scattered in the thickened neointima. In Nobori- or Ultimaster-implanted calcified lesions within 4 months after the procedure, remarkable detachment of polymer coating resulted in severe inflammatory reaction consisting of macrophages and lymphocytes. Conclusions: Polymer disruption may result in nonuniform drug distribution that may allow neointimal hyperplasia in the DES-implanted lesions. Moreover, polymer cracking may induce adverse and interrelated effects such as local inflammation and amplified cellular response, followed by very late stent thrombosis. Compared with polymer around the stent struts, delamination of abluminal polymer might occurr more easily when it is delivered through a calcified coronary artery.

Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD) were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD), field emission scanning electron microscope (FESEM) and high resolution transmission electron microscope (HRTEM). Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g) and pore diameter (6.7 nm) of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

Effect of Porous Activated Charcoal Reinforcement on Mechanical and In-Vitro Biological Properties of Polyvinyl Alcohol Composite Scaffolds

The present work focused on developing an innovative composite material by reinforcing polymer matrix with highly porous activated charcoal. Polyvinyl alcohol-activated charcoal (PVA-AC) composite scaffolds were developed by varying the AC concentrations (0, 0.5, 1, 1.5, 2 and 2.5 wt%) in PVA matrix by freeze drying method. The developed scaffolds were characterized for their physicochemical, mechanical and in-vitro biological properties. In addition, the effect of AC on the attachment, proliferation and differentiation of osteoblast MG 63 cells was evaluated by scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) activity assay and alizarin red stain-based (ARS) assay. All the PVA-AC composite scaffolds exhibited good bioactivity, hemocompatibility and protein adsorption properties. The scaffolds with high AC concentration (2.5 wt%) showed controlled drug release kinetics that are suitable for long term healing. The mechanical properties of all the PVA-AC composite scaffolds were improved when compared to the pure PVA scaffold. The high porosity, swelling degree and hydrophilicity of PVA-AC composite scaffolds facilitated cell attachment and proliferation. This is due to porous AC present in the sample that supported the osteoblast differentiation and formed mineralized nodules without the addition of any extra agents. From the above studies, it can be concluded that PVA-AC composite scaffolds are promising biomaterials for bone tissue engineering applications.

Water dispersible siloxane nanogels: a novel technique to control surface characteristics and drug release kinetics.

Amphiphilic, water-dispersible, crosslinked siloxane nanogels were synthesized via a free radical solution polymerization and then applied as optically clear, functional coatings on the surface of lens substrates to demonstrate the feasibility of siloxane-nanogels to generate covalently tethered surfaces on intraocular lens substrates. Siloxane nanogels were synthesized from 3-(trimethoxysilyl)propyl methacrylate and polyethylene glycol diacrylate and subsequently chain-end functionalized with mercaptosuccinic acid to yield a clear, water-dispersible nanogel. The nanogels were then spin-coated onto lens substrates as a coating and covalently tethered via a two-part interfacial redox polymerization using N'N'-tetramethylethylenediamine and ammonium persulfate. Covalently crosslinked, stable nanogel coatings on the lens substrate were shown to increase the hydrophilicity of the material surfaces while maintaining optical clarity, with >85% of white light transmittance. No significant changes were observed in the cytocompatibility, refractive index and mechanical properties of the substrate before and after the coatings were generated. The coatings were also modified to facilitate the sustained release of an anti-inflammatory drug dexamethasone in which >90% of the incorporated drug within the nanogel was released within 5 days, thereby demonstrating the feasibility of this approach to also enable the multi-day sustained delivery of an active pharmaceutical agent (API) at therapeutically relevant doses.

Core–shell SrTiO3:Yb3+,Er3+@mSiO2 nanoparticles for controlled and monitored doxorubicin delivery

The investigation of nano-carriers with controllable and trackable drug release kinetics has attracted worldwide attention for theranostic protocols with catabatic side effects.

Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers

Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0–∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa.

Controlled Drug Delivery: Historical perspective for the next generation

The modern day drug delivery technology is only 60years old. During this period numerous drug delivery systems have been developed. The first generation (1950–1980) has been very productive in developing many oral and transdermal controlled release formulations for clinical applications. On the other hand, the second generation (1980–2010) has not been as successful in generating clinical products. This is in large part due to the nature of the problems to overcome. The first generation of drug delivery technologies dealt with physicochemical problems, while the second struggled with biological barriers. Controlled drug delivery systems can be made with controllable physicochemical properties, but they cannot overcome the biological barriers. The third generation (from 2010) drug delivery systems need to overcome both physicochemical and biological barriers. The physicochemical problems stem from poor water solubility of drugs, large molecular weight of peptide and protein drugs, and difficulty of controlling drug release kinetics. The biological barriers to overcome include distribution of drug delivery systems by the body rather than by formulation properties, limiting delivery to a specific target in the body. In addition, the body's reaction to formulations limits their functions in vivo. The prosperous future of drug delivery systems depends on whether new delivery systems can overcome limits set by human physiology, and the development process can be accelerated with new ways of thinking.

Back Cover: Synthesis of CaTiO3 Nanofibers with Controllable Drug‐Release Kinetics (Eur. J. Inorg. Chem. 27/2015)

Back Cover: Synthesis of CaTiO₃ Nanofibers with Controllable Drug‐Release Kinetics (Eur. J. Inorg. Chem. 27/2015)

Targeting tumor vasculature with aptamer-functionalized doxorubicin-polylactide nanoconjugates for enhanced cancer therapy.

An A10 aptamer (Apt)-functionalized, sub-100 nm doxorubicin-polylactide (Doxo-PLA) nanoconjugate (NC) with controlled release profile was developed as an intravenous therapeutic strategy to effectively target and cytoreduce canine hemangiosarcoma (cHSA), a naturally occurring solid tumor malignancy composed solely of tumor-associated endothelium. cHSA consists of a pure population of malignant endothelial cells expressing prostate-specific membrane antigen (PSMA) and is an ideal comparative tumor model system for evaluating the specificity and feasibility of tumor-associated endothelial cell targeting by A10 Apt-functionalized NC (A10 NC). In vitro, A10 NCs were selectively internalized across a panel of PSMA-expressing cancer cell lines, and when incorporating Doxo, A10 Doxo-PLA NCs exerted greater cytotoxic effects compared to nonfunctionalized Doxo-PLA NCs and free Doxo. Importantly, intravenously delivered A10 NCs selectively targeted PSMA-expressing tumor-associated endothelial cells at a cellular level in tumor-bearing mice and dramatically increased the uptake of NCs by endothelial cells within the local tumor microenvironment. By virtue of controlled drug release kinetics and selective tumor-associated endothelial cell targeting, A10 Doxo-PLA NCs possess a desirable safety profile in vivo, being well-tolerated following high-dose intravenous infusion in mice, as supported by the absence of any histologic organ toxicity. In cHSA-implanted mice, two consecutive intravenous infusions of A10 Doxo-PLA NCs exerted rapid and substantial cytoreductive activities within a period of 7 days, resulting in greater than 70% reduction in macroscopic tumor-associated endothelial cell burden as a consequence of enhanced cell death and necrosis.

Controlled drug release from pharmaceutical nanocarriers

Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics.

Submicron polymeric particles prepared by vibrational spray-drying: Semisolid formulation and skin penetration/permeation studies

Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.

Fabrication and characterization of monodisperse PLGA–alginate core–shell microspheres with monodisperse size and homogeneous shells for controlled drug release

Monodisperse PLGA–alginate core–shell microspheres with controlled size and homogeneous shells were first fabricated using capillary microfluidic devices for the purpose of controlling drug release kinetics. Sizes of PLGA cores were readily controlled by the geometries of microfluidic devices and the fluid flow rates. PLGA microspheres with sizes ranging from 15 to 50μm were fabricated to investigate the influence of the core size on the release kinetics. Rifampicin was loaded into both monodisperse PLGA microspheres and PLGA–alginate core–shell microspheres as a model drug for the release kinetics studies. The in vitro release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid release patterns, although smaller PLGA cores had a higher release rate and a shorter lag phase. The shell could modulate the drug release kinetics as a buffer layer and a near-zero-order release pattern was observed when the drug release rate of the PLGA core was high enough. The biocompatibility of PLGA–alginate core–shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line and no obvious cytotoxicity was found. This technique provides a convenient method to control the drug release kinetics of the PLGA microsphere by delicately controlling the microstructures. The obtained monodisperse PLGA–alginate core–shell microspheres with monodisperse size and homogeneous shells could be a promising device for controlled drug release.

Fractal structure determines controlled release kinetics of monolithic osmotic pump tablets

To calculate the fractal dimension values of felodipine osmotic pump tablets during drug dissolution and to characterize the mechanism of the controlled drug release kinetics through three-dimensional fractal data. Three-dimensional fractal values of volume (Df,volume ) and surface (Df,surface ) of the tablet core were calculated based on the box counting method. During the process of release of felodipine, both Df,volume and Df,surface were within the range of 2-3 and then changed markedly after a period of 3.0 h release, corresponding to extensive changes in entire shape, interior porous channels and surface structure of the tablet core. The curve of Df,volume mirrored that for tablet volume, however the curve of Df,surface was quite different from that of the surface area. Results showed that values of Df,surface correlated well with the drug release rate. Df,surface was found to be an efficient fractal parameter that could be used to characterize the complex changes to the tablet core that take place during drug release. The fractal dimension can be used as a quantitative indicator reflecting the drug release performance and be regarded as a key indicator for the quality control of oral controlled drug delivery systems.