Characterization Of Drug Release Research Articles

Novel Rhinological Application of Polylactic Acid-An In Vitro Study.

A novel approach to the treatment of sinusitis is the use of nasal stents. The stent is loaded with a corticosteroid, which prevents complications in the wound-healing process. The design is such that it will prevent the sinus from closing again. The stent is 3D printed using a fused deposition modeling printer, which enhances the customization. The polymer utilized for the purpose of 3D printing is polylactic acid (PLA). The compatibility between the drugs and polymers is confirmed by FT-IR and DSC. The drug is loaded onto the polymer by soaking the stent in the drug's solvent, known as the solvent casting method. Using this method, approximately 68% of drug loading is found to be achieved onto the PLA filaments, and a total of 72.8% of drug loading is obtained in terms of the 3D-printed stent. Drug loading is confirmed by the morphological characteristics of the stent by SEM, where the loaded drug is clearly visible as white specks on the surface of the stent. Drug release characterization is conducted by dissolution studies, which also confirm drug loading. The dissolution studies show that the release of drugs from the stent is constant and not erratic. Biodegradation studies were conducted after increasing the rate of degradation of PLA by soaking it in PBS for a predetermined duration of time. The mechanical properties of the stent, such as stress factor and maximum displacement, are discussed. The stent has a hairpin-like mechanism for opening inside the nasal cavity.

Characterization of Drug Release from Mesoporous SiO2-Based Membranes with Variable Pore Structure and Geometry.

Transdermal drug delivery systems (TDDSs) play important roles in therapy due to distinct advantages over other forms and types of drug application. While common TDDS patches mainly consist of polymeric matrices so far, inorganic carriers show numerous advantages such as high mechanical stability, possible re-use and re-loading of drugs, and a broad chemical compatibility with therapeutically relevant compounds and chemical enhancers. Mesoporous glasses can be prepared in different monolithic shapes, and offer a particularly wide range of possible pore volumes, pore diameters, and specific surface areas. Further, they show high loading capacities and favorable physical, technical, and biological properties. Here, we explored for the first time monolithic SiO2-based carriers as sustained release systems of therapeutic drugs. In an ideally stirred vessel as model system, we systematically analyzed the influence of pore diameter, pore volume, and the dimensions of glass monoliths on the loading and sustained release of different drugs, including anastrozole, xylazine, imiquimod, levetiracetam, and flunixin. Through multilinear regression, we calculated the influence of different parameters on drug loading and diffusion coefficients. The systematic variation of the mesoporous glass properties revealed pore volumes and drug loading concentrations, but not pore diameter or pore surface area as important parameters of drug loading and release kinetics. Other relevant effectors include the occurrence of lateral diffusion within the carrier and drug-specific properties such as adsorption. The structure–property relationships derived from our data will allow further fine-tuning of the systems according to their desired properties as TDDS, thus guiding towards optimal systems for their use in transdermal drug applications.

Improved Biocompatibility of TiO2 Nanotubes via Co-Precipitation Loading with Hydroxyapatite and Gentamicin

The antibacterial properties of titanium make it useful for clinical applications. Hydroxyapatite (HA) is widely utilized as a coating on orthopedic implants to improve osteointegration. Titanium oxide nanotubes (TNT) are recognized as a promising solution for local antibiotic therapy in bone implants. It is demonstrated that the utilization of HA-coated titanium can improve the biocompatibility of bone implants. This research aims to examine the antibacterial properties and biocompatibility of the TiO2 nanotubes by loading HA and gentamicin. In vitro testing, the characterization of drug release, cell adhesion and proliferation, bacteria culture, and antibacterial tests were conducted. During the in vivo experiments, Staphylococcus aureus was implanted into the femur of rats. The animals were sacrificed at four weeks followed by microbiological and clinical assessments on the bone, which were conducted by removing the implants followed by agar plating. The in vitro cell incubation demonstrated that the TiO2 nanotubes loaded with hydroxyapatite and gentamicin had better cellular compatibility compared to Cp–Ti. In addition, in vitro elution testing showed that gentamicin was released from the hydroxyapatite/TiO2 nanotubes for as long as 22 days. The release time was much longer than the TNT loaded with gentamicin at only 6 h. All animals in the gentamicin/HA/TNT group were free of infection compared to those in the Cp–Ti, TNT, and HA/gentamicin/TNT groups. There was a considerable reduction in the rates of infection among the rats with gentamicin-HA-TNT coatings compared to standard titanium. These results indicated that the co-precipitation of gentamicin and HA loading using the TNT method provided a novel prophylactic method against prosthetic infections and other biomedical applications.

Influence of the test method on in vitro drug release from intravitreal model implants containing dexamethasone or fluorescein sodium in poly (d,l-lactide-co-glycolide) or polycaprolactone

Sustained intravitreal dexamethasone (DX) administration with the FDA and EMA approved Ozurdex® implant is indicated for the treatment of macular edema and non-infectious uveitis. Since drug release after intravitreal application cannot be determined in vivo in human eyes, the characterization of drug release in vitro in addition to animal models is of great importance. The aim of this study was to provide information about the influence of the test method on the in vitro drug release from intravitreal model implants. The following test methods were used: a shaking incubator experiment in reagent tubes, the small volume USP apparatus 7, the Vitreous Model (VM) and a system simulating the impact of movement on the VM (Eye Movement System, EyeMoS). Cylindrical model implants composed of DX and PLGA (poly (d,l-lactide-co-glycolide)) and additional polycaprolactone (PCL) implants containing fluorescein sodium (FS) as a model substance were produced by hot melt extrusion and were cut to a length of approximately 6 mm. Drug release was studied in ringer buffer pH 7.4 and in a modified polyacrylamide gel (PAAG) as vitreous substitute. In combination with the VM, the shape, the gel structure and a partial liquefaction (50%) were simulated in vitro.Swelling, disintegration, fragmentation, surface enlargement and changes in shape of the PLGA model implants were observed during the drug release study. We experienced that not each of the test methods and media were suitable for drug release studies of the PLGA implants. Marked differences in the release profiles were observed depending on the employed test method. These results emphasize the necessity to understand the underlying in vivo processes and to transfer the knowledge about the release determining factors into reliable in vitro test systems.

Characterization of drug release from fibrin gels loaded with different pharmaceutical and experimental doxorubicin formulations.

Local delivery of anticancer drugs represents a desirable type of treatment. Nevertheless, characteristics such as availability, biocompatibility, ease of operation, and efficacy sometimes represent difficult to overcome hurdles. Fibrin gels (FBGs) may be attractive biomaterials for local treatment when loaded with different chemotherapeutics or with polymer-anticancer-drug conjugates and nanoparticles. These components, linked together, might represent candidates to counteract local recurrences or reduce the volume of inoperable tumors. In the present study we analyzed the features of in vitro release of different formulations of doxorubicin (DOXO) from FBGs, and in vivo FBGs degradation. In vitro DOXO release from FBGs was studied as a function of thrombin and Ca2+ ion concentrations. DOXO was loaded in FBGs either alone or pre-incorporated in nanoparticles characterized by different physical features. The FBGs in vivo degradation was analyzed after sc or ip positioning. Our results suggest that each of the factors involved in the FBGs preparation may have different effects on drug release. In particular, the fibrinogen (FG) concentration and, above all, the DOXO formulation were found to have the greatest impact. Not surprisingly, we have also found a longer permanence in vivo of FBGs prepared at the highest thrombin, Ca2+ ion, and FG concentrations. The aim of this work was to study the effect of several conditions for preparing drug delivery systems based on FBGs loaded with different clinical or experimental formulations of DOXO. Our data identify some of these modalities that will be tested in vivo to evaluate their antitumor activity.

In vitro release studies of insulin from lipid implants in solution and in a hydrogel matrix mimicking the subcutis

Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective of the current work was to investigate the feasibility of developing UV imaging-based in vitro methods enabling visualization and characterization of drug release and transport of protein therapeutics intended for subcutaneous administration. Specifically, the objectives were to prepare lipid implants providing sustained release of the model protein insulin and investigate the release into 0.5% (w/v) agarose hydrogels, pH7.40, using UV imaging- and a gel sampling-based release testing method. These results were compared to insulin release into well agitated buffer solution. Irrespective of the applied in vitro release method, the insulin release from Sterotex implants with a drug load of 20% (w/w) was faster as compared to the release from implants with a load of 10% (w/w), most likely due to the higher porosity of the implants with increasing drug load. Insulin release from 10% (w/w) implants into agitated solution was faster as compared to release into agarose hydrogel. This was ascribed to the additional mass transfer resistance provided by the agarose hydrogel. Interestingly, the release profiles of insulin from implants with an initial drug load of 20% (w/w) obtained by the three in vitro methods were relatively similar. The gel-based methods, in particular UV imaging, enable monitoring local drug concentrations in the vicinity of the implant over time thereby facilitating assessment of, e.g., sink conditions. The study highlights that the selection of the in vitro release method should take into account various factors including mass transport, drug stability, data analysis and simplicity of the methodology.

Prediction and characterization of drug release in a multi-drug release system

A new drug delivery system (DDS) was prepared by electrospinning and multi-layered coating methods. Lactobacillus was used as a target drug for release in the large intestine. Lactobacillus was incorporated into polyvinyl alcohol-based electrospun fibers. Alginate and chitosan were then used to coat these fibers to protect and deliver lactobacillus to the large intestine. The multi-layered coating procedure was carried out at various coating times to determine the optimal coating amount in human digestion conditions. The drug-release experiment was conducted using an in vitro model of human digestion processes. Chitosan and alginate were released by dissolving in acid and neutral conditions, respectively. Lactobacillus was then released in a large intestine model by the hydrogel swelling effects of PVA-based electrospun fibers. The drug-release behavior was predicted by calculated equations for optimized coating times. Eventually, the lactobacillus was effectively delivered to the target large intestine by chitosan and alginate coating and was released by PVA hydrogel swelling.

A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery

The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first-pass metabolism. A tri-layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri-layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). The novel tri-layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery.

Precautions in using global kinetic and thermodynamic models for characterization of drug release from multivalent supports

AbstractBuilding-up a detailed kinetic model for drug release from various supports is a difficult task, especially when chemical reactions take place, accompanied by adsorption-desorption and diffusion steps. Often, semi-empirical release models derived from theoretical formulations of the transport process and system characteristics are employed. Their parameters have limited validity as they are dependent on the support, drug-ligand properties, and release conditions. However, they are often used for a quick simulation and design of drug delivery systems with a controlled release correlating the model parameters with the system characteristics and release conditions. Detailed information allows elaboration of an extended mechanistic model; the bias in the predictions introduced on various levels of model simplification is presented in this paper. A case study of a chemically activated ligand release in human plasma from a multivalent dendrimeric support is approached, pointing out the imprecision introduced by the gradual simplification of an extended model as well as the low reliability of the prediction when using various semi-empirical global models.

Modeling and characterization of drug release from glutinous rice starch based hydrogel beads for controlled drug delivery

Purpose: To identify the potential of Assam Bora rice in modulation of drug release from the formulated matrix devices and demonstrate its utility in pharmaceutical drug carrier systems. Methods: The hydrogel microbeads were prepared by an industrially feasible conventional ionotropic gelation method using the blends of pregelatinized Bora rice along with sodium alginate as mucoadhesive backbone. The potential of proposed natural polymer in modulation of drug release from the formulated microbeads was investigated through in vitro dissolution test conducted as per SUPAC-MR guidelines provided by FDA. Data obtained from in vitro release studies were fitted to various kinetic equations to find out the kinetics and mechanism of drug release from fabricated microbeads. Results: The microbeads were almost spherical, discreet and free flowing in a size range of about 0.726±0.008 mm to 1.16±0.009 mm. The different formulations had variable correlation with the different kinetic models under the different release environments. Conclusion: Assam Bora can be a promising option for mucoadhesive controlled drug delivery systems as natural substance. Keywords: Drug delivery, Bora rice starch, Release kinetics, Natural polymer.

Electron microscope characterization of drug release from methacrylic acid-ethyl acrylate copolymer-coated cross-linked alginate-gelatine beads

Drug release from alginate-based beads is generally a fast process influenced by parameters such as bead production technique and drug physicochemical properties. In a previous report new cross-linked alginate-gelatin beads were developed, with the ability to successfully prolong drug release. The present work is focused on scanning electron microscopy analysis of the morphological modifications of cross-linked alginate-gelatin beads occurring throughout enteric coating with a methacrylic acid-ethyl acrylate copolymer and in vitro release studies. The coating material remains unchanged in gastric pH conditions irrespective either of the irregular thickness of the coating layer or related changes observed in the inner matrix. In phosphate buffer pH 7.4 the coating dissolves immediately and the cross-linked matrix tends to swell influencing drug release. However, beads maintained their shape throughout the dissolution test, presenting a prolonged drug release profile. The cross-linking bonds contribute to the particle keeping its shape throughout release. Microscopical analysis confirms that matrix modification by the cross-linking reaction is crucial for the controlled release of the model drug (pindolol) from alginate beads.

Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets

Abstract The purpose of this study was to implement the concepts of percolation theory in the characterization of drug release from hydrophilic matrix tablets. Percolation theory is a powerful statistical tool that enables mathematical insight into geometrically complex and disordered systems. Matrix tablets are effective substrate for the implementation of percolation theory because of their inherent disordered structure. The objective was to predict percolation thresholds of polyethylene oxide and polyacrylic polymers in diclofenac sodium hydrophilic matrices. Matrix tablets were prepared using polyethylene oxide or polyacrylic acid as matrix forming materials and diclofenac sodium was used as a model drug substance. Ten formulations with different drug/excipient ratios were prepared using the direct compression method. Dissolution studies were performed using the paddle apparatus method. For estimating percolation threshold the change of the kinetic parameters in aspect to the volumetric fraction of excipient plus initial porosity of the tablets was studied. Observed critical points with sudden changes in behavior of kinetic parameters can be attributed to the percolation thresholds. Percolation threshold is found to be 60.22% v/v polyethylene oxide + initial porosity and 39.94% v/v polyacrylic acid + initial porosity. The results obtained demonstrate that percolation theory can be used to design and develop matrix tablet formulations. Determination of percolation threshold is a useful tool for preparing robust formulations.

Characterization of Drug Release and Diffusion Mechanism Through Hydroxyethylmethacrylate/Methacrylic Acid pH-Sensitive Hydrogel

Hydroxyethylmethacrylate/methacrylic acid copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk free radical polymerization method. The permeability studies of this pH-sensitive hydrogel to drugs with different water solubilities showed a water-content dependent diffusion or pore mechanism for ephedrine HCl (water-soluble model drug), whereas, a partition or solute-diffusion mechanism for indomethacin (a water-insoluble drug) was seen. Data analysis of release tests, according to the swelling interface number and Peppas equation for ephedrine HCl in pH 7.4, showed a biexponential model kinetic, whereas in pH 1.2 a swelling-controlled mechanism was seen. Indomethacin was released by an anomalous or non-Fickian release kinetics.

Characterization of drug release from diltiazem-loaded polylactide microspheres prepared using sodium caseinate and whey protein as emulsifying agents

The influence of milk protein emulsifying agents on the characteristics, particularly drug release, of polylactide microspheres was investigated. Diltiazem loaded polylactide (PL) microspheres were successfully prepared using the dairy proteins, sodium casinate (SC) and whey protein isolate (WPI) as the emulsifying agents. Microspheres were characerized in terms of microsphere yield, electron microscopy, particle size, drug loading, DSC and XRD analysis and drug release. The yields of microspheres obtained were 53-63% and were independent of the emulsifying agent used. SEM revealed that, regardless of the emulsifying agent employed, the microspheres were of good sphericity, but the surface appearance of the microspheres was not the same in all cases. The milk proteins resulted in microspheres approximately half the size of those obtained with methylcellulose (MC). Significant differences in drug loading were observed between the three emulgents, the MC systems giving the highest values. Release profiles were sigmoidal in shape and were well fitted to the equation ln (x/1-x) = k·t - k·tmax, reflecting degradation controlled drug release. The parameter k increased with drug loading, while tmax decreased. The relationships between the release parameters [P(k and tmax)] and loading (L) could be quantified by equations of the form P = a·LN, N being negative in the case of tmax. Apart from the effect on loading efficiency, neither SC nor WPI appeared to significantly alter drug release. The quantitative relationships observed in this study may have more general application in quantifying drug release from drug polymer composites at low loadings where polymer degradation controls drug release.

Characterization of Drug Release from Liposomal Formulations in Ocular Fluid

The successful application of liposomes in topical ophthalmic drug delivery requires knowledge of vesicle stabilization in the presence of tear fluid. The release of procaine hydrochloride (PCH) from large unilamellar liposomes in the presence of simulated tear fluid was studied in vitro as a function of bilayer lipid content and tear protein composition. Reverse-phase evaporation vesicles were prepared from egg phosphatidylcholine, stearylamine or dicetyl phosphate, and cholesterol. The relationship between lipid composition and encapsulation efficiency, vesicle size, drug leakage upon storage at 4°C, and the release of PCH-loaded liposomes was studied. The encapsulation efficiency was found to be dependent upon the lipid composition used in the liposome preparation. In particular, phosphatidylcholine vesicles containing cholesterol and/or charged lipids had a lower entrapment efficiency than liposomes prepared with phosphatidylcholine alone. However, the drug release rate was reduced significantly by inclusion of cholesterol and/or charged lipids in the liposomes. The release kinetics of the entrapped agent seemed to be a biphasic process and the drug-release in both simulated tear fluid (STF) and pH 7.4 phosphate buffered saline (PBS) solutions followed pseudo first-order kinetics in the early stage of the release profile. The drug-release appeared to be diffusion and/or partition controlled. Drug release from liposomes into STF, pH 7.4 PBS, and five different modified tear formulations was also evaluated. While serum-induced leakage is attributed to high-density lipoprotein-mediated destabilization, it was determined that lactoferrin might be the protein component in tear fluid that has the primary influence on the liposome-entrapped drug release rate.Five local anesthetics, benoxinate, proparacaine, procaine, tetracaine, and benzocaine were entrapped in liposomal vesicles by a reverse-phase evaporation (REV) technique. The release of these structurally similar topical anesthetics entrapped in positively charged liposomes (egg phosphatidylcholine, stearylamine, and cholesterol in a 7:2:1 molar ratio) was evaluated in a simulated tear fluid and pH 7.4 phosphate buffered saline solution. The liposomes appeared to be useful carriers for these drugs to retard their in vitro release in tear fluid and perhaps sustain or control their release in the eye for better therapeutic efficacy. An analysis of the release data demonstrated that for this series of drugs, drug partition coefficient has the largest effect on release rate, with molecular weight exhibiting a smaller effect. Release rate was found to decrease with increased lipophilicity or increased molecular weight.

Entrapment of bioactive compounds within native albumin beads: IV. Characterization of drug release from polydisperse systems

A heuristic approach is used to identify the mathematical model best describing the release of a drug from a single particle in a polydisperse system. The method uses only experimental measures of particle size distribution and total release from the dispersion as a function of time. The routine is based on the observation that in the first 40% of total drug release the volume-surface diameter of the distribution, d vs, can be used as a single diameter representing the entire population to estimate model dependant release parameters. This property was tested in four different single particle release models having distributions of varying standard deviation; narrow, intermediate, and wide. In its application to drug imbedded in a microsphere, the particle size distribution of the system was measured and the volume-surface diameter determined. Release from the population was measured under sink conditions. The first 40% was fit (SAS) using d vs and assuming different mechanisms to be operating; release parameters characteristic of the assumed single particle mechanism were thus generated. Since only one of the assumed mechanisms should be operating, when the parameter estimates for each are used over a larger time frame (beyond 40%) in conjunction with the effects expected for individual particles of known size via measured distribution, the best single particle model should be that one giving the best overall fit. For norgestrel in a serum albumin microsphere, the single particle model best describing release was matrix diffusion of drug from a particle surrounded by a hydrodynamic layer.