Initial Drug Release Research Articles

The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles.

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

Effect of Granulation Methods on Drug Release Studies in Sustained Release Matrix Tablets of a Poorly Soluble Drug prepared using Synthetic Polymers

Vomiting or emesis is the abnormal emptying of stomach and upper part of intestine through esophagus and mouth. It occurs due to stimulation of the emetic (vomiting) centre situated in the medulla oblongata. Domperidone, a D2 receptor antagonist has antiemetic and prokinetic action is used as a model drug in the present work to prepare Sustained release matrix tablets using various synthetic polymers like Eudragit and HPMC K15 M. The tablets are designed to have a pH dependent release profile in order to prevent initial drug release in the stomach to reduce the possible gastro-irritant and ulcerogenic effects of the drug. Different polymer and diluent concentrations and various compression techniques like wet granulation technique and direct compression techniques were used in order to release the contents of the tablets in a sustained manner over a certain period of time. Domperidone is BCS Class II drug and its solubility was enhanced by preparing solid dispersions using solvent evaporation technique. In the present work solid dispersions containing drug and polymer mixture in the ratio 1:1 was further formulated into tablets by incorporating various synthetic polymers in three different concentrations. The tablets were prepared using different granulating techniques. Formulation (F3) containing drug and polymers in the ratio 1:1 prepared by wet granulation technique could sustain the drug release over a period of 12h and hence considering all the post compression parameters it was optimized as the better formulation. FTIR, DSC, X-Ray Diffraction, SEM studies were performed for optimized solid dispersion mixture and also the optimized formulation.
 Keywords: Solubility enhancement, Solid dispersions, Solvent Evaporation, Wet granulation, Direct Compression.

Carboxymethyl fenugreek galactomannan-g-poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide)-clay based pH/temperature-responsive nanocomposites as drug-carriers.

The current study dealt with the synthesis and characterization of carboxymethyl fenugreek galactomannang-g-poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide)-bentonite [CFG-g-P(NIPA-co-MBA)-BEN] based nanocomposites (NCs) as erlotinib (ERL)-delivery devices for lung cancer cells to suppress excessive cell proliferation. The blank NCs exhibited outstanding biodegradability and pH/temperature-dependent swelling profiles, which were significantly influenced by their BEN contents (0-20%). The molar mass (M¯c) between the crosslinks of these NCs was declined with temperature. The composite architecture of these scaffolds was confirmed by XRD, FTIR, TGA, DSC and SEM analyses. The corresponding ERL-loaded matrices (F-1-F-3) portrayed outstanding drug encapsulation efficiency (DEE, 93-100%) with zeta potential between -8 and -16mV and diameter between 615 and 1258nm. These formulations demonstrated sustained ERL elution profiles (Q8h, 62-98%) with an initial burst release of drug. The drug dissolution pattern of the optimized matrices (F-3) obeyed first-order kinetic model and was driven by Fickian diffusion. The mucin adsorption behavior of F-3 was best fitted to Freudlich isotherms. The ERL-loaded formulation suppressed A549 cell proliferation and promoted apoptosis to a greater extent than the pristine drug, as detected by cellular uptake analysis, MTT cytotoxicity test and AO/EB staining assay.

Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells

Cubosomes, a product of nanobioengineering, are self-structured lipid nanoparticles that act like drug-loaded theranostic probes. Here, we describe a simple method for the preparation of combinatorial drug-loaded cubosomes with, proof-of-principle, therapeutic effect against cancer cells, along with diagnostic capabilities. Anticancer drugs cisplatin and paclitaxel were loaded in the cubosomes in combination. The cubosomes were coated with a layer of poly-Ɛ-lysine, which helped avoid the initial burst release of drug and allowed for a slow and sustained release for better efficacy. Cubosomes were imaged by transmission electron microscope, and their dispersion analyzed in vitro by differential scanning calorimetric and X-ray diffractogram studies. The microscopic images depicted spherical polyangular structures, which are easily distinguishable. The analyses revealed that the drug is uniformly dispersed all through the cubosomes. Further characterization was carried out by zeta-potential measurement, in vitro release, and entrapment efficiency studies. The in vitro studies established that the coating of cubosomes successfully reduced the burst release of drugs initially and confirmed a slow, sustained release over increased time. Comparative cytotoxicity of coated, uncoated, and blank cubosomes was evaluated, using human hepatoma HepG2 cell line, and the formulations were found to be entirely nontoxic, similar to the blank ones. The therapeutic efficiency of the cubosomes against HeLa cells was confirmed by the impedance measurement and fluorescent imaging. Furthermore, the reduction in impedance in cells treated with coated combinatorial cubosomes proved the impairment of HeLa cells, as confirmed by fluorescence microscopy.

Levonorgestrel release rates measured through analysis of two-rod contraceptive explants

ObjectiveThe objective was to characterize and compare in vivo rates of levonorgestrel (LNG) release from Sino-implant (II) and Jadelle® contraceptive implants. Study designWe sampled 48 Sino-implant (II) and 49 Jadelle® explant sets for residual LNG content from participants treated for up to 51 months in a randomized contraceptive efficacy trial in the Dominican Republic (DR). Additional Sino-implant (II) explants were obtained from 8 women who became pregnant in the DR trial and 10 who contributed 3 to 5 years of use in a cohort study in China. Baseline LNG loads were estimated from five unused implant sets per device type. Release profiles were estimated using mixture models that captured initial burst fractions and compared with efficacy and pharmacokinetics data from the DR trial. ResultsEstimated baseline LNG loads for Sino-implant (II) and Jadelle® were 142.8 mg and 150.5 mg, respectively (vs. the labeled 150 mg). There was an initial burst release of drug (5.6% and 7.9%, respectively) followed by an exponential decrease in LNG content evident for each device. Release rates were significantly lower for Sino-implant (II) throughout the treatment period, with estimated rates after 3 years of 24.2 mcg/day and 29.0 mcg/day for Sino-implant (II) and Jadelle®, respectively. The estimated Sino-implant (II) rate after 3 years was similar to the predicted rate after 5 years (23.6 mcg/day) for Jadelle® (rate ratio: 1.03; 95% confidence interval: 0.92–1.13). ConclusionsSino-implant (II) LNG release rates were significantly lower than Jadelle® with Sino-implant (II) rates through year 3 comparable to Jadelle® rates through year 5. These results reinforce the 3-year duration of action for which Sino-implant (II) was prequalified by the World Health Organization. ImplicationsThis analysis confirms the WHO prequalification of Sino-implant (II) for 3 years of use and supports different durations of action for Jadelle® and Sino-implant (II). It provides additional evidence that this approach can complement efficacy trials in determining duration of action of hormonal contraceptives in general.

Melt electrohydrodynamic 3D printed poly (ε-caprolactone)/polyethylene glycol/roxithromycin scaffold as a potential anti-infective implant in bone repair.

Implanted scaffold or bone substitute is a common method to treat bone defects. However, the possible bone infection caused by orthopaedic surgery has created a challenging clinical problem and generally invalidate bone repair and regeneration. In this study, a poly (ε-caprolactone) (PCL)/polyethylene glycol (PEG)/roxithromycin (ROX) composite scaffold was prepared via melt electrohydrodynamic (EHD) 3D printing. Fourier transform infrared spectroscopy (FTIR) spectroscopy was performed to verify the existence of PEG and ROX in the scaffolds. By water contact angle measurement, the addition of both PEG and ROX was found to improve the hydrophilicity of the scaffolds. By in vitro drug release assay, the PCL/PEG/ROX scaffolds showed an initial burst drug release and subsequent long-term sustained release behaviour, which is favourable for the prevention and treatment of bone infections. The antibacterial assays against E. coli and S. aureus demonstrated that the composite scaffold with ROX possessed effective antibacterial activity, especially for S. aureus, the main cause of bone infection. The immunostaining and MTT assay with human osteoblast-like cells (MG63) indicated that cells showed good viability and growth on the scaffolds. Therefore, the melt EHD 3D printed PCL/PEG/ROX scaffold could be a promising anti-infective implant for bone tissue engineering.

Electrospun thymol-loaded porous cellulose acetate fibers with potential biomedical applications.

Drug toxicity induced by burst release has become a great challenge in clinical therapeutics. In most studies of drug delivery, great attention has been given to achieving sustained drug release by enhancing the surface hydrophobicity of drug carriers. However, many of them improved surface hydrophobicity through chemical methods, which could be toxic and time-consuming. This paper aims at providing a facile way to improve surface hydrophobicity of drug carriers. Here, a kind of porous cellulose acetate (CA) fibrous membranes containing different amount of thymol (THY) for sustained drug release were prepared, by co-electrospinning technique. The ellipse-shaped nanopores were generated on the surfaces of electrospun fibers in situ, which trapped a part of air at the interface and thus enhanced the hydrophobicity of fibrous membranes. The in vitro drug release results showed that the porous THY-loaded fibrous membranes had slower initial drug release and extended drug release time, compared with nonporous THY-loaded fibrous membranes. In addition, the higher specific surface area of porous THY-loaded CA fibrous membranes contributed to a higher drug utilization ratio. Antibacterial results demonstrated that porous THY-loaded CA fibrous membranes possessed more effective inhibition against S. aureus and E. coli, with only 0.07% and 0.09% of bacterial survival rate, respectively. Furthermore, the combination of porous surface structure with a controllable drug release improved the proliferation of L929 cells, indicating a better cytocompatibility. Taken together, the porous THY-loaded CA fibrous membrane offer significant promise as novel wound healing materials.

An Optimized Surfactant-Based PEG-PLCL In Situ Gel Formulation For Enhanced Activity Of Rosuvastatin In Poloxamer-Induced Hyperlipidemic Rats.

BackgroundInjectable in situ gel (ISG) systems suffer from high initial drug release that may result in toxic effects.ObjectiveThis work aimed to develop an injectable sustained release rosuvastatin (RSV) ISG formulation with minimum initial drug burst and improved hyperlipidemic efficacy.MethodsSix formulation factors that affect RSV release after 0.5, 2 and 24 hrs have been screened and the significant ones were optimized utilizing an experimental design tool. The optimum ISG formulation components were physicochemically characterized. Kinetic treatment, dissolution efficiency and mean dissolution time were investigated for the developed ISG formulations. Pharmacodynamic effects of the optimized ISG formulation were studied and compared to ISG formulation loaded with free RSV and to a marketed oral drug product.ResultsThe concentration polylactide-co-ε-caprolactone (25: 75), the surfactant hydrophilic lipophilic balance (HLB) and the ratio of surfactant to polyethylene glycol 400 were significantly affecting the release of RSV during the first 24 h. Physicochemical characterization demonstrated complete dispersion of RSV in the polymeric matrix with slight changes in the drug crystalline structure. The optimized formulation demonstrated acceptable syringeability, good flow rate and was able to extend the in vitro drug release for 34 days. The ISG formulations complied with Weibull model. Pharmacodynamic study revealed a sustained reduction in the lipid profile that lasted for 21 days with a marked decrease in the lipid level during the first 24 hrs from the ISG system loaded with free RSV.ConclusionThe optimized RSV ISG formulation could be considered a promising strategy due to a reduction in dosing frequency and enhancement in hypolipidemic efficacy.

A modified hydrophobic ion-pairing complex strategy for long-term peptide delivery with high drug encapsulation and reduced burst release from PLGA microspheres

Poor encapsulation and high initial burst were two major obstacles for the water-soluble peptide drug loaded microspheres preparation using the industrial emulsification method. In the present study, we hypothesized that the hydrophobic ion-pairing (HIP) complex strategy with a further healing of the pores within the microspheres may improve drug encapsulation and initial burst release. DSS was chosen as the most suitable one among the three test ion-pairing agents (SDS, DSS and STC) due to its high binding efficiency with drug and reversible dissociation capacity in presence of counter ions. The formation of HIP complex between octreotide acetate and DSS successfully reversed the highly water-soluble nature of the drug. A specific S/O/W method was adopted to encapsulate such drug containing HIP complex. The encapsulation efficiency of the drug was greatly improved compared with the conventional W1/O/W2 method (from 44% to 90%). Under the optimal healing conditions (the healing time 6 h, temperature 40 °C and 4% DEP content), the pores within the microspheres were effectively healed. Initial burst amount of octreotide acetate in S/O/W microspheres decreased to 3.56%. The pore healing effect was further confirmed by the scanning electron microscopy and fluorescence microscopy results. In the process of testing the drug release performance of such new strategy in vitro and in vivo, a more satisfactory single phase release profile with sustained and steady drug release was observed. These results suggested that the modified HIP strategy could be a promising platform for water-soluble peptide encapsulation with high encapsulation efficiency, low initial burst and stable drug release mechanism.

Doxycycline containing hydroxyapatite ceramic microspheres as a bone-targeting drug delivery system.

Drug delivery technology is a promising way to enhance the therapeutic efficacy of drugs. The purpose of this study is to evaluate the physical and chemical properties of hydroxyapatite ceramic microspheres loaded with doxycycline (HADOX), their effects on in vitro osteoblast viability, and their antimicrobial activity, and to determine the effects of DOX on the healing of rat sockets after tooth extraction. The internal microsphere porosity was sensitive to the treatment used to adsorb DOX onto microsphere surface; HA microspheres without DOX presented 26% of pores, whereas HADOX0.15 microspheres presented 52.0%. An initial drug release of 49.15 μg/ml was observed in the first 24 hr. The minimal inhibitory concentration (MIC) tested against Enterococcus faecalis demonstrated that bacterial growth was inhibited for up to 7 days. Results of cell viability and cell proliferation did not indicate statistical differences in the metabolic activity of HADOX samples relative to HA without DOX microspheres (p > .05). After 1 week, a discreet inflammation reaction was observed in the control group, and after 6 weeks, newly-formed bone was observed in the HADOX0.15 (p < .05). The HADOX did not interfere in the bone repair and controlled the early inflammatory response. HADOX could be a promising biomaterial to promote bone repair in infected sites.

Cyclic β-(1, 2)-glucan blended poly DL lactic co glycolic acid (PLGA 10:90) nanoparticles for drug delivery

Our group had previously reported the encapsulation efficiency of cyclic β-(1, 2)-glucan for various drugs. The current study is aimed at evaluating the use of glucan as a drug carrier system by blending with poly lactic-co- glycolic acid (L:G = 10:90). Nanoparticles of glucan (0.5, 5, 10 and 20 wt %) blended with PLGA and gentamicin were synthesized. Encapsulation efficiency was higher for the blends (93% with 20 wt % of glucan) than the PLGA alone (79.8%). The presence of glucan enhanced both the biodegradability, and biocompatibility of PLGA. Degradation of the nanoparticles in vitro, was autocatalytic with an initial burst release of active drug and the release profile was modeled using the Korsmeyer-Peppas scheme. In vivo studies indicated that the drug released from the blends had high volume of distribution, and greater clearance from the system. Pharmacokinetics of the drug was predicted using a double exponential decay model. Blending with PLGA improved the drug release characteristics of the cyclic β-(1, 2)-glucan.

DESIGN AND DEVELOPMENT OF TOPICAL HYDROGEL FORMULATION OF IRBISARTAN

Objective: Irbesartan is an antihypertensive with limited bioavailability. The objective of the study was to develop controlled release matrix tablets of irbisartan drug.&#x0D; Methods: Tablets were prepared by wet granulation process. Result: In vitro drug release study revealed that HPMC causes initial burst release of drug hence combining HPMC sustained the action for 8 h (95.92±0.57% release). Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism for drug release. Compared to conventional tablets, the release of model drug from these HPMC matrix tablets was prolonged, leading to achieve an effective therapy with a low dosage of the drug, to reduce the frequency of medication. The pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension.&#x0D; Results: Compatibility Studies In order to investigate the possible interactions between irbesartan and distinct polymers and/or diluents, FT-IR and DSC studies were carried out. FT-IR results proved that the drug was found to be compatible with excipients as wave numbers are almost similar for pure drug and also drug excipients mixture. In picture 1 and 2. DSC studies indicate that chosen excipients for the formulation were found to be compatible with the active ingredient as the melting endothermic peaks are in the range of 250-320 °C which is same as the melting point of irbisartan.&#x0D; Conclusion: Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150–300 mg once daily confers a lasting effect over 24 h, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide.

Learning from Peptides to Access Functional Precision Polymer Sequences.

Functional precision polymers based on monodisperse oligo(N-substituted acrylamide)s and oligo(2-substituted-α-hydroxy acid)s have been synthesized. The discrete sequences originate from a direct translation of side-chain functionality sequences of a peptide with well-studied properties. The peptide was previously selected to solubilize the photosensitizer meta-tetra(hydroxyphenyl)chlorin. The resulting peptidomimetic formulation additives preserve the drug solubilization and release characteristics of the parent peptide. In some cases, superior properties are obtained, reaching up to 40 % higher payloads and 27-times faster initial drug release.

Surface Wettability Modulated by Surfactant and Its Effects on the Drug Release and Absorption of Fenofibrate Solid Dispersions.

The objective of this study is to explore the surface wettability modulated by a surfactant and its effects on the drug release and absorption of fenofibrate solid dispersions (FF SDs). Both the polyvinylpyrrolidone/sodium lauryl sulfate (PVP/SLS) coprecipitate and FF SDs were prepared by solvent evaporation method. The contact angle of PVP/SLS coprecipitate with various PVP/SLS weight ratios was determined to screen out the suitable content of SLS incorporated in FF SDs. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) was used to analyze the surface composition of the PVP/SLS coprecipitate, suggesting that SLS molecules were prone to concentrate on the carrier surface. The physicochemical characteristics of FF, PVP, SLS, FF SDs, and FF physical mixtures (PMs) were evaluated by thermal analysis, XRD, FTIR, and SEM, which revealed that FF was molecularly dispersed in SDs. The interaction between SLS and PVP or FF confirmed by FTIR would affect the surface morphology of SDs. Finally, the contact angle of FF SDs was measured to explore the effects of surface wettability on the dissolution behavior and drug absorption of FF SDs. The interesting thing is that the wettability of the PVP/SLS coprecipitate was positively related to that of FF SDs. The improved wettability of FF SDs or the PVP/SLS coprecipitate by adding SLS contributed to the slight enhancement of initial drug release and absorption, which implied that wettability would be a promising tool in the formulation studies.

Transport characteristics in a novel in vitro release model for testing the performance of intra-articular injectables

There is a need for bio-predictive and well-characterized in vitro release models in the development of intra-articular depot formulations. Here, the commercially-available Scissor system, a membrane-based two-compartment release testing instrument, was applied to characterize the transport and release of the drug diclofenac employing conditions intended to mimic transport in the synovial joint. The fate of hyaluronic acid and human serum albumin, the main bio-relevant components incorporated in the system, was investigated. A promising strategy for providing sustained drug release upon intra-articular administration are lipid-based preformulations forming non-lamellar liquid crystalline phases in situ. The usefulness of the Scissor system for investigating the initial drug release from these delivery systems was evaluated. The diclofenac release rate upon injection of an aqueous solution was influenced by the composition of the injection site matrix, i.e. the hyaluronic acid content. Hyaluronic acid and human serum albumin were found to escape from the donor compartment into the acceptor medium through the employed polycarbonate membrane. Sustained diclofenac release was obtained by formation of highly viscous liquid crystalline phases upon injection of the lipid-based preformulations. The study shows the feasibility and potential of the Scissor system for testing initial release of intra-articular depot formulations of low-molecular-weight drug compounds.

Formulation development and characterization of highly water-soluble drug-loaded extended-release pellets prepared by extrusion–spheronization technique

The objectives of current study were (a) to prepare extended-release plain (without polymers) and matrix pellets of itopride hydrochloride (ITP) by extrusion and spheronization technique, (b) to control the initial fast release of drug from the matrix pellets by coating using ethylcellulose, Eudragit® RL/RS100 (2:1), and Kollicoat® SR 30D, and (c) to investigate the influence of different types and concentration of coating polymers on release of highly water-soluble drug. The plain pellet contained microcrystalline cellulose and lactose without polymer, whereas matrix pellet formulations were composed of hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M) and ethylcellulose (EC 7 cps). Matrix pellet formulations failed to control the drug release, up to targeted period of 12 h. Five pellet formulations—one without polymer (F1) and one from each polymer category (F4, F7, F10, and F13)—were screened out for coating using different types and levels of polymers. The DDSolver (an add-in software for MS Excel) was used to analyze the dissolution profile data for drug release kinetics. However, drug release from pellet formulation (F7) containing HPMC as a matrix former and coated with EC followed zero-order kinetics (R2 = 0.897–0.998). The release mechanism of EC-coated formulations F7, F10, and F13 was non-Fickian diffusion (anomalous transport), whereas F1 and F4 were Fickian diffusion mechanism. The stability studies of all 5% EC-coated ITP pellet formulations were conducted at room and accelerated temperature as per ICH guidelines, and results were found satisfactory. It is concluded that ethylcellulose other than Eudragit® RL/RS100 (2:1) and Kollicoat® SR 30D was found to be an excellent release controlling agent for ITP which showed good controlled-release characteristics.

Highly Soluble Drugs Directly Granulated by Water Dispersions of Insoluble Eudragit® Polymers as a Part of Hypromellose K100M Matrix Systems

The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).

Mechanically-Activated Microcapsules for 'On-Demand' Drug Delivery in Dynamically Loaded Musculoskeletal Tissues.

Delivery of biofactors in a precise and controlled fashion remains a clinical challenge. Stimuli-responsive delivery systems can facilitate 'on-demand' release of therapeutics in response to a variety of physiologic triggering mechanisms (e.g. pH, temperature). However, few systems to date have taken advantage of mechanical inputs from the microenvironment to initiate drug release. Here, we developed mechanically-activated microcapsules (MAMCs) that are designed to deliver therapeutics in an on-demand fashion in response to the mechanically loaded environment of regenerating musculoskeletal tissues, with the ultimate goal of furthering tissue repair. To establish a suite of microcapsules with different thresholds for mechano-activation, we first manipulated MAMC physical dimensions and composition, and evaluated their mechano-response under both direct 2D compression and in 3D matrices mimicking the extracellular matrix properties and dynamic loading environment of regenerating tissue. To demonstrate the feasibility of this delivery system, we used an engineered cartilage model to test the efficacy of mechanically-instigated release of TGF-β3 on the chondrogenesis of mesenchymal stem cells. These data establish a novel platform by which to tune the release of therapeutics and/or regenerative factors based on the physiologic dynamic mechanical loading environment, and will find widespread application in the repair and regeneration of numerous musculoskeletal tissues.

Formulation, Development and Evaluation of Bilayer Tablet of Flurbiprofen

In the Study of Formulation of Bilayer Tablet of Flurbiprofen the Following Materials Using sodium starch glycolate as immediate release and HPMC K15 in different ratios as release retardant materials using a wet granulation method. All tablets exhibited good physical properties with Respect to appearance, content uniformity, hardness, weight variation and Invitro dissolution data show at increasing proportions Of sodium starch glycolate for immediate release whereas HPMC K15sustaineddrugreleaserate. The bilayer tablets showed an initial release of drug In about1hr, then sustaining the release for 12h, The kinetic analysis of dissolution data showed that release was observe din these tablets. When data was fitted to the Higuchi model. Bilayer tablets of flurbiprofen can be successfully formulated Using sodium starch glycolate and HPMC K15 in different ratios as release retardant materials employing a wet granulation method.

Preparation and Characterization of Itraconazole- or Miconazole-Loaded PLGA Microspheres

The purpose of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres (MS) loaded with itraconazole (ITCZ) or miconazole (MCZ) under different evaporation temperatures (25 or 40°C) using an oil-in-water emulsion solvent evaporation method in order to evaluate the initial burst release of drug. Loading efficiencies were comparatively good and the diameters of prepared drug-loaded PLGA MS were around 20 µm in all formulations. The release rates of ITCZ-PLGA MS prepared at 40°C showed a significantly restricted release profile compared with the corresponding ITCZ-PLGA MS prepared at 25°C. This difference in release rate of ITCZ was thought to be caused by the self-healing effect of PLGA, as the glass transition temperature of PLGA is around 40°C. With respect to the MCZ-PLGA MS, the initial burst release was similar in formulations prepared at both 25 and 40°C. Scanning electron microscope results suggested that the initial burst release was due to the localization of MCZ on the surface of MCZ-PLGA MS at higher concentrations. Differential scanning calorimetry measurements suggested complete amorphization of MCZ in MCZ-PLGA MS, whereas crystalline ITCZ was detected in the ITCZ-PLGA MS. This complete amorphization of MCZ is considered to be one of the reasons for the initial burst release.