Synthesis and Characterization of Metal‐doped Chitosan‐Hydroxyapatite Composites for the Tuning of Properties: Evaluating Antibacterial Activity and Drug Release

Controlled drug delivery is useful because it allows obtaining better drug product, effectiveness, reliability and safety. Hydrogel are one of the upcoming classes of polymer-based controlled release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogel also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogel (a class of polymeric systems) in controlled drug delivery, and their application in pH-responsive, drug release. Hydrogel show minimal tendency to adsorb proteins from body fluids because of their low interfacial tension. Further, the ability of molecules of different sizes to diffuse into (drug loading) and out of (drug release) hydrogel allows the possible use of dry or swollen polymeric networks as drug delivery systems for oral, nasal, buccal, rectal, vaginal, ocular and parenteral routes of administration. Hydrogel also terms ‘intelligent gels’ or ‘smart hydrogel’. The smartness of any material is the key to its ability to receive, transmit or process a stimulus, and respond by producing a useful effect. This review highlights the use of hydrogel (a class of polymeric systems) in controlled drug delivery, and their application in stimuli responsive, especially pH-responsive, drug release. In this review article, the various aspects of pharmaceutical microemulsin where compile together and the target audience are specifically the M. pharm and B .pharm student so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

Modifying the drug-release capacity of titanium implants is essential for maintaining their long-term functioning. Titanium dioxide nanotube (TNT) arrays, owing to their drug release capacity, are commonly used in the biomaterial sphere. Their unique half open structure and arrangement in rows increase the drug release capacity. However, their rapid drug release ability not only reduces drug efficiency but also produces excessive local and systemic deposition of antibiotics. In this study, we designed a tantalum-coated TNT system for drug-release optimization. A decreased nanotube size caused by the tantalum nanocoating was observed through SEM and analyzed (TNT: 110 nm, TNT-Ta1: 80 nm, TNT-Ta3: 40 nm, TNT-Ta5: 20 nm, TNT-Ta7: <5 nm). XPS analysis revealed the distribution of the chemical components, especially that of the tantalum element. In vitro experiments showed that the tantalum nanocoating enhanced cell proliferation; in particular, TNT-Ta5 possessed the best cell viability (about 1.18 of TNT groups at 7d). It also showed that the tantalum nanocoating had a positive effect on osteogenesis (especially TNT-Ta5 and TNT-Ta7). Additionally, hydrophilic/hydrophobic drug (vancomycin/raloxifene) release results indicated that the TNT-Ta5 group possessed the most desirable sustained release capacity. Moreover, in this drug release system, the hydrophobic drug showed more sustained release capacity than the hydrophilic drug (vancomycin: sustained release for more than 48 h, raloxifene: sustained release for more than 168 h). More importantly, TNT-Ta5 is proved to be an appropriate drug release system, which possesses cytocompatibility, osteogenic capacity, and sustained drug release capacity.

Tuning drug loading and release properties of diatom silica microparticles by surface modifications

Carbon nanomaterials as drug carriers: Real time drug release investigation

Molecular interactions, internal structure and drug release kinetics of rationally developed polymer–lipid hybrid nanoparticles

PurposeAn efficient drug-delivery system was prepared based on graphene oxide using a facile and one-step strategy for controlling the release of anticancer drugs.MethodsFabrication of single-layer graphene oxide (GO) sheets was carried out by both modified and improved Hummers method. Biocompatible hyperbranched polyglycerol (HPG) was grafted on the surface of GO through the ring-opening hyperbranched polymerization of glycidol. Various ratios of GO and glycidol were used for polymer grafting. An anticancer drug, quercetin (Qu), was loaded into modified GO via noncovalent interactions.ResultsPolymer grafting on the surface of GO sheets was confirmed by results obtained from Fourier-transform infrared and Raman spectroscopy, thermogravimetric analysis, energy-dispersive X-ray and X-ray spectroscopy, scanning electron microscopy, and atomic force microscopy. It was revealed that polymerization increased d-spacing between the basal planes. In addition, as a hydrophilic polymer, HPG improved the stability and dispersion of GO sheets in biological solutions and endowed extra drug-loading capacity for the sheets. The effect of hyperbranched structure on drug loading and release was investigated by comparing drug loading and release for HPG-modified GO and linear PPO-modified GO. Our experiments indicated high drug-loading capacity (up to 185%), and excellent encapsulation efficiency (up to 93%) for HPG-GO compared to linear PO-grafted GO. The release profile of Qu under various pH levels exhibited controlled and sustained drug release without an initial burst effect for HPG-GO, suggesting that an acidic solution could facilitate drug release. HPG-GO did not show any cytotoxicity on the MCF7 cell line in different concentrations during 72 hours’ incubation. Uptake and entrance of HPG-GO into the cells were verified by determining the intracellular amount of Qu by high-performance liquid chromatography.ConclusionA combination of the unique properties of GO and the biodegradable polymer polyglycerol revealed high drug-loading capacity, pH-dependent drug release, and cytocompatibility with HPG-GO, thus introducing it as a promising nanocarrier for anticancer drug delivery.

The aim of controlled drug delivery is to manage the time and site of drug release according to the patients’ need.In this paper, Micro Electro-Mechanical Systems (MEMS) technology is described.This technology employs microelectronics and microprocessor circuits in order to reach individualized, targeted and controlled drug release and would construct the future drug delivery systems. Introduction: Controlled drug delivery systems are the state of the art in drug delivery technology with the goal of controlling the drug release at right time and site to satisfy the patient’s pathophysiological requirements. In spite of great improvements in this field, it still remains an open research area.MEMS employs sophisticated systems in a small scale. In last few decades, this technology has increasingly attracted the researchers’ attention due to its successful miniaturization of complicated drug delivery systems to address unmet dosing requirements more precisely.MEMS drug delivery systems are fabricated using the microelectronics and microprocessor circuits of highly-advanced technology. This provides the opportunity to implement several drug reservoirs and billions of electronic devices in few millimeters. Methods and Results: In this study, MEMS technology is introduced along with describing the fabrication process. Two main categories of MEMS devices including internal and transdermal devices and their applications in drug delivery systems are presented. Various actuators applied in these devices are described, including electrical, electrochemical, electromechanical, and electrothermal types. Finally, emerging technologies and prospects are briefly reviewed. Conclusions: MEMS techniques can be easily combined with microprocessors and sensors to implement an intelligent system which can determine the proper drug dosage and release time according to the signals received by biosensors. When placed inside the body, biocompatibility and biofouling issues should be well-considered, since the device will remain in the patient’s body for a long time. Therefore, MEMS technology seems to be the future aspect of targeted drug delivery systems. Key words: Micro Electro-Mechanical Systems (MEMS), targeted drug delivery, actuator, internal device, transdermal device

Studies have frequently shown that successful drug release from amorphous solid dispersions (ASDs) is highly dependent on polymer dissolution. Underpinning drug release from ASDs is a series of complex steps involving solvent penetration into the glassy core, gel formation and swelling, and colloid formation and release. The objective of this study was to predict ritonavir (RTV) and polymer release from ASDs of RTV and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) from discs with varying geometries based solely on solvent penetration. Using vacuum compression molding, ASD discs containing RTV/PVPVA were fabricated with drug load ranging from 0 to 50%. Three disc geometries were 8 mm thin disc, 20 mm thin discs, and 8 mm thick discs, where 8 and 20 mm denoted disc diameter. Hence, ASDs varied in drug load and geometry. ASDs were subjected to microscope-enabled disc dissolution system (MeDDiS) testing (i.e., simultaneous imaging and dissolution from disc side) as well as USP II dissolution testing, which allowed release from additional surfaces. Five disc models were derived based on solvent penetration and varied in releasing surface areas [i.e., disc side model, disc top and bottom (T&B) model, disc top model, sunken disc model, and total disc model]. Solvent penetration rate was visually observed to be rate-limiting and was quantitatively measured from MeDDiS imaging, where the solvent penetration rate was approximately the same across drug loads from 0 to 25% and across disc geometries. Predicted drug and polymer release was obtained from each of the five disc dissolution models for each of the three disc geometries, including base-case models that reflected visual observations of disc dissolution (i.e., disc side model for MeDDiS and either sunken disc model or total disc model for USP II). There was excellent agreement between predicted and observed ASD drug (and polymer) release. In particular, the observed drug and polymer release from MeDDiS closely matched the disc side model, reflecting the base-case of only release from the disc side. Meanwhile, release from USP II testing closely matched the base-cases of the sunken disc model (for 8 mm thin and 8 mm thick discs) and the total disc model (for 20 mm discs). However, predicted profiles were slightly faster than the observed profiles, indicating solvent penetration was rate-dominating, although not the only barrier to drug and polymer release. Results here indicate successful model predictions of drug release from a well-studied ASD drug/polymer pair, which has promise to aid the understanding of less well-studied ASDs.

Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers.

The aim of this study was to probe the dissolution mechanisms of amorphous solid dispersions (ASDs) of a poorly water-soluble drug formulated with a hydrophilic polymer. Ritonavir (RTV) and polyvinylpyrrolidone/vinyl acetate (PVPVA) were used as the model drug and polymer, respectively. ASDs with drug loadings (DLs) from 10 to 50 wt % were prepared by solvent evaporation. Surface-normalized dissolution experiments were carried out using Wood's intrinsic dissolution apparatus, and both drug and polymer release were quantified. ASDs at or below 25% DL showed rapid, complete, and congruent (i.e., simultaneous) release of the drug and polymer with dissolution rates similar to that of the polymer alone. The highest drug loading at which congruent release was observed is termed the limit of congruency (LoC) and occurred at 25% DL for RTV-PVPVA. The ASD with 30% DL showed an initial lag time, followed by a period of congruent release. At later times, the release of drug and polymer became incongruent with polymer releasing faster than drug. Higher DL ASDs (40 and 50%) showed slow release of both drug and polymer, whereby the drug release rate was similar to that of the neat amorphous drug. In cases where the release of the ASD components was congruent or close to congruent, the drug concentration exceeded the amorphous solubility, and liquid-liquid phase separation (LLPS) occurred with the formation of colloidal, drug-rich species. Solid state analyses of the ASD tablet surface by infrared spectroscopy and scanning electron microscopy revealed that the partially dissolved tablet surface remains smooth, and drug-polymer miscibility is retained at low DLs; whereas, at a very high DL, the surface is porous and enriched with amorphous drug. In concert, these observations suggest that ASD dissolution and drug release at low DLs is governed primarily by hydrophilic polymer; whereas, at high DLs, amorphous drug controls dissolution. Fluorescence microscopy images of thin ASD films suggested that ASDs at or below the LoC remain homogeneous even after exposure to water. In contrast ASDs with DL above LoC undergo, to various extents, water-induced amorphous-amorphous phase separation (AAPS) leading to demixing of the drug and polymer. Correlating the observations of the dissolution study with the solid state data suggest that the ASDs with DLs higher than the LoC undergo AAPS in the hydrating matrix on the surface of the dissolving solid during dissolution, leading to separation of drug and polymer, the formation of a drug-rich interface, and hence, incongruent and/or slow release of the components. In contrast, low DL ASDs dissolve before AAPS occurs. The competition between these two parallel and competing processes on the surface of ASD solids, i.e., dissolution and AAPS, thus dictates the overall release characteristics of the ASD formulations, which is one of the most important considerations in designing formulations with superior dissolution and absorption.

Polymeric microspheres have gained widespread application as drug eluting depots. Typically, drug-loaded polymeric microspheres are prepared by oil-in-water emulsification which yields a product with a broad size distribution. The aim of the present study was to investigate the properties of different size-fractions of drug-loaded microspheres, in order to delineate whether particle size governs drug loading efficiency and release profile. Gefitinib-loaded PLGA-based microspheres were prepared using an oil-in-water solvent evaporation method and wet-sieved to obtain well-defined size fractions of 5 ± 1, 32 ± 4, 70 ± 3, and 130 ± 7 μm, respectively. The average drug loading of unfractionated microspheres was 6.3 ± 0.4% w/w, while drug loading of sieved fractions ranged from 2.4 ± 0.3 to 7.6 ± 0.9% w/w for smallest to largest microparticles. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis demonstrated that gefitinib was amorphously dispersed in the PLGA matrix, with no apparent shift in the Tg of PLGA indicating the absence of direct molecular interactions of the drug and polymer due to the formation of small drug particles embedded in PLGA. In vitro drug release was studied with microspheres embedded in dextran hydrogels to avoid their aggregation during the incubation conditions. Microspheres smaller than 50 μm showed rapid diffusion-based release reaching completion within 2 days when particles have not degraded yet. Larger microspheres, however, showed a sigmoidal release pattern that continued for three months in which diffusion (early stage) as well as particle erosion (later stage) governed drug release. Scanning electron microscopy (SEM) and polymer degradation data showed that larger microspheres degraded faster than smaller ones, which is in line with autocatalytic PLGA degradation upon acidification within the core of microparticles. In conclusion, we showed that different size-fractions of drug-loaded microspheres showed quite distinct drug loading and release kinetics. Control of microparticle size by fractionation is therefore an important determinant for obtaining well-defined and reproducible sustained release depots.

Qualitative evaluation of the mechanism of release of matrix sustained release dosage forms by measurement of polymer release

3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release

Structure and Drug Release in a Crosslinked Poly(Ethylene Oxide) Hydrogel

Osmotic Pellet System Comprising Osmotic Core and In-Process Amorphized Drug in Polymer–Surfactant Layer for Controlled Delivery of Poorly Water-Soluble Drug