Total Drug Release Research Articles

EFFICIENT DRUG CARRIER FOR ACETYLSALICYLIC ACID FROM CHITOSAN-BASED COMPOSITES PREPARED WITH MONTMORILLONITE, CELLULOSE, AND HYDROXYAPATITE

In this study, chitosan-based hydroxyapatite/chitosan (HAP/CHI), cellulose/chitosan (CEL/CHI) and montmorillonite/chitosan (MMT/CHI) composites were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Thermogravimetric Analysis (TGA). Acetylsalicylic acid (ASA) was used as a drug for loading and desorption studies to determine the release behavior of the synthesized composites. The maximum adsorption capacities (qe) were obtained as 251.5 mg/g, 197.7 mg/g and 288.95 mg/g for HAP/CHI, CEL/CHI and MMT/CHI, respectively. In vitro release studies of ASA from the composites HAP/CHI, CEL/CHI, and MMT/CHI were carried out phosphate buffer solution (PBS) and gastric juice (GJ). In the intestinal medium (PBS) controlled drug release continued for 72 hours (4320 minutes), and burst release was observed in the first 5 minutes in all composites. 19.16%, 47.15% and 37.32% of the active ingredient from HAP/CHI, CEL/CHI and MMT/CHI composites, respectively, were released in the first 5 minutes. After 5 minutes, the release slowed down and became more controlled for all three composites. At the end of the release, the highest releasing composite was CEL/CHI, with 95.77% ASA release. A total drug release of 87.48% was achieved with MMT/CHI and 87.37% with HAP/CHI. In the gastric environment (GJ) Controlled drug release continued for 72 hours (4320 minutes), and burst release was observed in the first 5 minutes in all composites. 52.51%, 72.30% and 44.87% of the active ingredient from HAP/CHI, CEL/CHI and MMT/CHI composites, respectively, were released in the first 5 minutes. After 5 minutes, the release slowed down and became more controlled for all three composites. At the end of the release, the highest releasing capacity was found with the CEL/CHI composite, with 96.05% ASA release. A total drug release of 93.26% was achieved with HAP/CHI and 84.89% with MMT/CHI.

Modelling the controlled drug release of push-pull osmotic pump tablets using DEM

The push-pull osmotic pump tablet is a promising drug delivery approach, offering advantages over traditional dosage forms in achieving consistent and predictable drug release rates. In the current study, the drug release process of push-pull osmotic pump tablets is modelled for the first time using the discrete element method (DEM) incorporated with a microscopic diffusion-induced swelling model. The effects of dosage and formulation design, such as delivery orifice size, drug-to-polymer ratio, tablet surface curvature, friction between particles and cohesion of polymer particles, on the drug release performance are systematically analysed. Numerical results reveal that an enlarged delivery orifice significantly increases both the total drug release and the drug release rate. Moreover, the larger the swellable particle component in the tablet, the higher the drug release rate. Furthermore, the tablet surface curvature is found to affect the drug release profile, i.e. the final drug release percentage increases with the increasing tablet surface curvature. It is also found that the drug release rate could be controlled by adjusting the inter-particle friction and the cohesion of polymer particles in the formulation. This DEM study offers valuable insights into the mechanisms governing drug release in push-pull osmotic pump tablets.

Fabrication of a Controlled-Release Core-Shell Floating Tablet of Ketamine Hydrochloride Using a 3D Printing Technique for Management of Refractory Depressions and Chronic Pain.

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150-160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting.

Minimizing pain in deer antler removal: Local anaesthetics in ZnO nanoparticle based collagen dressings as a promising solution

Antler removal in deer is a common practice for various purposes, including meat production and traditional medicine. However, the current industry practice using lidocaine as a local anesthetic has limitations, such as short duration of action and the potential for postoperative infections. In this study, we investigated the performance of a ZnO collagen nanocomposites loaded with local anesthetics to improve wound management and alleviate pain associated with antler removal in red deer. The research involved the preparation of collagen nanocomposites with local anesthetics and testing the drug release rates using in vitro drug release tests. Pharmacokinetic analysis was performed to evaluate the total drug release from the collagen matrix in red deer after velvet removal. Additionally, the analgesic efficacy of these collagen nanocomposite dressings was assessed after antler removal in red deer. Functionalized ZnO nanoparticles were incorporated into collagen fibers to enhance their mechanical stability and prolong drug release. The developed collagen nanocomposites aimed to slowly release local anesthetics and promote wound healing. The findings of this research could have significant implications for improving the pain management and wound healing associated with antler removal in deer. The results obtained from the in vitro drug release tests, pharmacokinetic analysis, and analgesic efficacy evaluations provide valuable insights into the understanding and development of novel approaches for antler removal procedures in red deer. The findings contribute to the advancement of knowledge in this field and lay the foundation for future implementation of improved techniques and protocols for antler removal.

An Automated Electroanalytical Method for the Drug Release Profiling of Liposomal Doxorubicin HCl Formulations

Liposomes have emerged as a drug delivery system for various chemotherapeutics providing enhanced bioavailability and reduced toxicity. In vitro drug release profiling of liposomal formulations is one of the essential tests for the premarket approval and post market quality control. We developed an automated electroanalytical method for drug release profiling of liposomal doxorubicin formulation. In this electroanalytical method, square wave voltammetry mode was selected to determine the released drug, the only redox-active analyte, by measuring the current at the pulsed potential ranges. Therefore, no separation from liposomal encapsulated doxorubicin is needed. This electroanalytical method provided a continuous drug release measurement for 24 h. The drug release increased as the release media pH and temperature increased. At 37 °C, the drug release increased from 7 % to 40 % when the pH increased from 5.5 to 7.4, In addition, at pH 6.5, as the temperature increased from 37 °C to 52 °C, total drug release increased by more than two-fold. Complete drug release (more than 80 %) was obtained at pH 6.5 and 52 °C in less than 3 h. The brand name and the two generic formulations showed similar drug release profile in all experimental conditions. This method is an alternative to traditional methods which require separation steps such as dialysis or solid phase extraction to quantitate released doxorubicin. This method may be further applied in the in vitro release testing of other liposomal formulations containing redox-active drug substances, e.g., liposomes encapsulating daunorubicin.

Development and evaluation of redox-responsive alginate–SS–ibuprofen derivative based anti-tumor target drug delivery system for the controlled release of doxorubicin

Nowadays, self-assembled polymeric micelles from amphiphilic polymer conjugates are urgently needed to enhance drug targeting and release efficiency. On account of the excellent properties of alginate and the redox-responsiveness of disulfide bonds, a redox-sensitive alginate–SS–ibuprofen derivative (LSA–SS–IBU) based anti-tumor target drug delivery system was created by attaching the hydrophobic ibuprofen (IBU) onto the hydrophilic alginate molecular skeleton through disulfide linkages for glutathione (GSH) triggered delivery of doxorubicin hydrochloride (DOX). The structure and self-assembly behavior of the synthesized LSA–SS–IBU was systematically evaluated by FT-IR spectrometer, 1H NMR spectrometer, fluorescence spectrophotometer (FM), transmission electron microscope (TEM) and dynamic light scattering (DLS). Furthermore, the in vitro release of drugs from the LSA–SS–IBU micelles loaded with DOX was examined, along with the assessment of their cytotoxicity to HeLa cells. The resultant LSA–SS–IBU had a critical micelle concentration (CMC) value of 0.19 mg/mL that was able to self-assemble into the spherical micelles with the particle size and zeta potential of 148.2 ± 4.3 nm (PDI = 0.25) and −47.2 ± 0.4 mV, respectively. At a mass ratio of 3:10 for DOX/LSA–SS–IBU, the LSA–SS–IBU micelles achieved drug loading ratio (DLR) and encapsulation efficiency (EE) values of 12.2 % and 46.3 %, respectively. Furthermore, the in vitro drug release study indicated that the total drug release percentage of the drug-encapsulated LSA–SS–IBU micelles in PBS with the presence of 10 mmol/L GSH for 12 h exceeded 67.0 %, demonstrating a substantial increase compared to that in GSH-free PBS. The in vitro cytotoxicity findings indicated that LSA–SS–IBU had good biocompatibility, while the IC50 value and the cell viability of DOX-loaded LSA–SS–IBU micelles cultured with HeLa cells for 48 h was 2.2 μg/mL and less than 20.1 %, respectively, which could significantly inhibit the growth of HeLa cells. Therefore, redox-responsive LSA–SS–IBU micelles had potential applications in cancer therapy for hydrophobic anti-tumor drug delivery.

Evaluation of Ibuprofen Prolonged Release of Biomedical PLA-PEG-PLA Hydrogel via Degradation Mechanism.

A micellar hydrogel has long been considered an intelligent hydrophobic drug delivery material. In this study, synthesized PLA1750-PEG1750-PLA1750 micellar hydrogel aims to encapsulate ibuprofen (IBU) in the core PLA hydrophobic of the micelle and prolong the drug release time by an injectable route. The structure and morphology of the PLA1750-PEG1750-PLA1750 copolymer hydrogel were demonstrated by 1H NMR and TEM data. The hydrogel also achieved a gel state at a high concentration of 25 wt.% under the physiological conditions of the body (37°C, pH 7.4). Besides, the biocompatibility test displayed that the hydrogel slightly affected mice after injection one week and fully recovered after four weeks. Furthermore, the in vitro degradation of the hydrogel showed apparent gel erosion after the first three weeks, which is related to the IBU release rate: slow for the first three weeks and then fast. As a result, the total drug release after three and four weeks was 18 wt.% and 41 wt.%, respectively. However, in the first 24 hours, the amount of the drug released was 10 wt.%, suggesting that the IBU drug diffused from the surface hydrogel to the buffer solution. These show that PLA1750-PEG1750-PLA1750 hydrogel can be a potential IBU drug delivery candidate.

DESIGN AND IN VITRO EVALUATION OF ACRIVASTINE AS ORODISPERSIBLE TABLET USING DIRECT COMPRESSION METHOD.

The aim: This study aimed to develop mouth-dissolving tablets of Acrivastine, an antihistamine medication, in order to increase its oral bioavailability. Materials and methods: Different super disintegrants, such as crospovidone, croscarmellose sodium, and sodium starch glycolate, were used to make Acrivastine oral dispersible tablets (ODTs). These super disintegrants were utilized in various concentrations. The formulation (F3) with 6% w/w crospovidone had a fast disintegration time (less than 30 seconds) and practically total drug release within 10 minutes. All of the formulations were made using the direct compression method and proper diluents, binders, and lubricants. Fourier transform infrared spectroscopy (FTIR) tests were used to investigate the drug-ex¬cipient interaction, and all formulations demonstrated improved drug-excipient compatibility. Results: The average weight of all formulations was between 175 and 180 mg. All formulations' hardness and friability were within acceptable ranges. Direct compression tablets had a hardness of 3.2 to 4 kg/cm2. All formulations were determined to have a friability of less than 1.0%. For oral dissolving tablets, the in vitro disintegration time is critical, and this time preferred to be < 60 seconds. The results also showed that crospovidone disintegrated after 24 seconds and sodium starch glycolate disintegrated in 40 seconds in vitro. Conclusions: When compared to croscarmellose sodium and sodium starch glycolate, crospovidone performs better as a super disintegrant. In comparison to other formula, tablets breakdown in the mouth in 30 seconds and have a maximum in vitro drug release time in 1-3 minutes.

Adsorbent Precoating by Lyophilization: A Novel Green Solvent Technique to Enhance Cinnarizine Release from Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS).

Solidification by high surface area adsorbents has been associated with major obstacles in drug release. Accordingly, new approaches are highly demanded to solve these limitations. The current study proposes to improve the drug release of solidified self-nanoemulsifying drug delivery systems (SNEDDS) to present dual enhancement of drug solubilization and formulation stabilization, using cinnarizine (CN) as a model drug. The solidification process involved the precoating of adsorbent by lyophilization of the aqueous dispersion of polymer-adsorbent mixture using water as a green solvent. Then, the precoated adsorbent was mixed with drug-loaded liquid SNEDDS to prepare solid SNEDDS. The solid-state characterization of developed cured S-SNEDDS was done using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro dissolution studies were conducted to investigate CN SNEDDS performance at pH 1.2 and 6.8. The solidified formulations were characterized by Brunauer-Emmett-Teller (BET), powder flow properties, scanning electron microscopy, and droplet size analysis. In addition, the optimized formulations were evaluated through in vitro lipolysis and stability studies. The cured solid SNEDDS formula by PVP k30 showed acceptable self-emulsification and powder flow properties. XRD and DSC revealed that CN was successfully amorphized into drug-loaded S-SNEDDS. The uncured solid SNEDDS experienced negligible drug release (only 5% drug release after 2 h), while the cured S-SNEDDS showed up to 12-fold enhancement of total drug release (at 2 h) compared to the uncured counterpart. However, the cured S- SNEDDS showed considerable CN degradation and decrease in drug release upon storage in accelerated conditions. The implemented solidification approach offers a promising technique to minimize the adverse effect of adsorbent on drug release and accomplish improved drug release from solidified SNEDDS.

Formulation and Evaluation of Solid-Self Nano Emulsifying Drug Delivery System of Darunavir

The main aim of this research article is to Formulate and Evaluate the S-SNEDDS of Darunavir. Darunavir is an anti-retroviral protease inhibitor which is in use from long time, but it has poor bioavailability because of poor aqueous solubility and extensive first pass metabolism, when used in the form of conventional dosage form. As it is a BCS Class II drug, which shows low solubility and high permeability. The S-SNEDDS of Darunavir was prepared to improve its oral bioavailability and its release rate was evaluated by in vitro release. The solubility of Darunavir in various oils was to decide and identify the oil phase of formulations. Different oils, surfactants and co-surfactants were screened for their ability to emulsify the selected oil. The pseudo ternary phase diagram was used to know the self -emulsification region of formulation. The optimized S-SNEDDS formulation contain Darunavir (150mg), Caproyl®90(50mg), Labrasol® and Transcutol® mix (45 mg). The data of the FTIR confirms that there is no interaction observed and the drug and excipients was compatible with each other. The developed SNEDDS formulations were examined for nano emulsifying capabilities, and the resulting nano emulsions were investigated for self-emulsification efficiency, dispersibility and in-vitro dissolution. Centrifugation tests, particle size distribution, heating cooling cycle, zeta potential, and freeze thaw cycling were performed on the optimised formulations to establish the stability of the produced SNEDDS formulation. Further produced S-SNEDDS micromeritics studies were done. The formulation was shown to significantly improve drug release, with total drug release occurring within 60 minutes. Darunavir self-emulsifying formulation was thus effectively produced.

Semi-solid extrusion 3D printing of starch-based soft dosage forms for the treatment of paediatric latent tuberculosis infection.

The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-solid extrusion (SSE) 3D printing. Corn starch was used for ink preparation using ISO as model drug. The inks were characterized physicochemically and their viscoelastic properties were assessed with rheological analysis. The morphology of the printed dosage forms was visualized with scanning electron microscopy and their textural properties were evaluated using texture analysis. Dose accuracy was verified before in-vitro swelling and dissolution studies in simulated gastric fluid (SGF). Starch inks were printed with good resolution and high drug dose accuracy. The printed dosage forms had a soft texture to ease administration in paediatric patients and a highly porous microstructure facilitating water penetration and ISO diffusion in SGF, resulting in almost total drug release within 45 min. The ease of preparation and fabrication combined with the cost-effectiveness of the starting materials constitutes SSE 3D printing of starch-based soft dosage forms a viable approach for paediatric-friendly formulations in low-resource settings.

3D-printed implantable devices with biodegradable rate-controlling membrane for sustained delivery of hydrophobic drugs

Implantable drug delivery systems offer an alternative for the treatments of long-term conditions (i.e. schizophrenia, HIV, or Parkinson’s disease among many others). The objective of the present work was to formulate implantable devices loaded with the model hydrophobic drug olanzapine (OLZ) using robocasting 3D-printing combined with a pre-formed rate controlling membrane. OLZ was selected as a model molecule due to its hydrophobic nature and because is a good example of a molecule used to treat a chronic condition schizophrenia. The resulting implants consisted of a poly(ethylene oxide) (PEO) implant coated with a poly(caprolactone) (PCL)-based membrane. The implants were loaded with 50 and 80% (w/w) of OLZ. They were prepared using an extrusion-based 3D-printer from aqueous pastes containing 36–38% (w/w) of water. The printing process was carried out at room temperature. The resulting implants were characterized by using infrared spectroscopy, scanning electron microscopy, thermal analysis, and X-ray diffraction. Crystals of OLZ were present in the implant after the printing process. In vitro release studies showed that implants containing 50% and 80% (w/w) of OLZ were capable of providing drug release for up to 190 days. On the other hand, implants containing 80% (w/w) of OLZ presented a slower release kinetics. After 190 days, total drug release was ca. 77% and ca. 64% for implants containing 50% and 80% (w/w) of OLZ, respectively. The higher PEO content within implants containing 50% (w/w) of OLZ allows a faster release as this polymer acts as a co-solvent of the drug.

Lipid Nanocarriers Overlaid with Chitosan for Brain Delivery of Berberine via the Nasal Route.

This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUCbrain/AUCblood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy.

Formulation and Evaluation of Fish Collagen Extract into Thin Films

Collagen is a macromolecule of connective tissues in animals and it is cosmopolitan in skin, bones, teeth, tendons, ligament, cartilage, eyes, blood vessels, gut and inter-vertebral discs. Collagen is attracting attention as a biomaterial with several properties such as inducing natural process of blood platelets, cell differentiation, and wound healing, through physical and chemical modifications. The present study was aimed to extract collagen from fish skin and formulate into collagen thin films. Fish collagen thin film was prepared using solvent casting method by using gelatin, sodium alginate, CMC, PEG and ferric oxide, and the formulations were named as F1 to F5. The prepared thin films were cut into strips of area 2X2 cm2 and evaluated for organoleptic evaluations, film weight, thickness, folding endurance, drug content of films, surface pH, disintegration time, in-vitro dissolution studies, moisture loss and uptake and stability studies. The results of the analysis parameters such as weight, thickness, percentage transparency, swelling property, surface pH and folding endurance depends on the concentration of sodium alginate and PEG used. Accelerated stability studies have not shown much remarkable changes in the reading of weight, disintegration time and surface pH, thus it indicates that temperature would not alter the properties of the thin film. From the results of percentage drug release collagen is released fast from F3 (60% in 10 min), and the total drug release was obtained in a span of 40 min, this formulation can be used for the preparation of thin films and F3 total drug release was obtained in 60 min

Electrospun poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan ternary nanofibers with antibacterial activity for treatment of skin infections

In recent years, there is an increasing attention on biocompatible electrospun nanofibers for drug delivery applications since they provide high surface area, controlled and sustained drug release, and they mimic the extracellular matrix. In the present study, tetracycline hydrochloride (TCH) antibiotic loaded poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan nanofibrous membranes were fabricated as a controlled drug delivery system. Poly(ω-pentadecalactone-co-ε-caprolactone) copolymer has been enzymatically synthesized in previous studies, thus it provides an originality to the membrane. Combination of a synthetic polymer, a protein, and a polysaccharide in order to obtain a synergetic effect is another novelty of this work and there exists limited examples for such electrospun membrane. Varied amounts of TCH was electrospun together with poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan (50/40/10 vol ratio) polymer blend (fiber diameters ranged between 85.7–225.2 nm) and several characterizations (morphological and molecular structure, wettability characteristics, and thermal behavior) were applied to examine the drug incorporation. Subsequently, in vitro drug release studies were conducted and mathematical modeling was applied for the detection of transport mechanism of drug. TCH release proceeded 14 days through an initial burst release in first hour and followed by a sustained release. 1% TCH-loaded sample was shown as optimal preparation with 96.5% total drug release and 11.8% initial burst release. TCH-loaded preparations demonstrated a good antibacterial activity against Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria and a limited effect (no inhibition zone observed below 3% TCH concentration) against Gram-negative (Escherichia coli) bacterium. Thus, TCH concentrations of ≥ 3% could be preferred to obtain a wide-spectrum effectiveness. The presented drug delivery system is suggested to be applied for treatment of skin infections as a wound dressing device.

PH-Dependent supersaturation from amorphous solid dispersions of weakly basic drugs.

In amorphous solid dispersions (ASDs), the chemical potential of a drug can be reduced due to mixing with the polymer in the solid matrix, and this can lead to reduced drug release when the polymer is insoluble in the dissolution media. If both the drug and the polymer composing an ASD are ionizable, drug release from the ASD becomes pH-dependent. The goal of this study was to gain insights into the pH-dependent solubility suppression from ASD formulations. The maximum release of clotrimazole, a weakly basic drug, from ASDs formulated with insoluble and pH-responsive polymers, was determined as a function of solution pH. Drug-polymer interactions in ASDs were probed using melting point depression, moisture sorption, and solid-state Nuclear Magnetic Resonance spectroscopy (SSNMR) measurements. The extent of solubility suppression was dependent on polymer type and drug loading. The strength of drug-polymer interactions was found to correlate well with the degree of solubility suppression. For the same ASD, the degree of solubility suppression was nearly constant across the solution pH range studied, suggesting that polymer-drug interactions in residual ASD solids was independent of solution pH. The total drug release agrees with the Henderson-Hasselbalch relationship if the suppressed amorphous solubility of the free drug is independent of solution pH. The mechanism of solubility suppression at different solution pHs appeared to be drug-polymer interactions in the solid-state, where the concentration of the free drugremains the same at variable pHs and the total drug concentration follows the Henderson-Hasselbalch relationship.

Porous silicon nitride–based drug delivery carrier

AbstractTetracalcium phosphate/monetite biocement was modified with the addition of 30 wt% highly porous silicon nitride/α‐tricalcium phosphate (α‐TCP) microgranules. The volume ratio of Si3N4 and α‐TCP in microgranules was 1:1 and showed good in vitro simulated body fluid bioactivity with precipitation of hydroxyapatite particles. The intention of addition of microgranules to the biocement was to have a carrier of drug, which can be released into the body in due time. Granules prepared by the freeze granulation of starting mixture of silicon nitride and calcium phosphate and subsequent sintering at 1100°C have a suitable pore structure for the foreseen use. The pore volume was almost 1000 mm3/g with the open porosity of 77 vol%. This porosity and the biocompatible composition of silicon nitride–based granules gave a chance to fabricate a suitable composite cement for dexamethasone (DMZ) drug release into the human body. An accelerated release of dexamethasone from composite cement was observed and the full amount of DMZ was released from the composite biocement after 10 days. The presented results are a good base to adjust the total drug release time by the mixing of an appropriate amount of drug infiltrated ceramic granules with the tetracalcium phosphate/monetite cement.

Synthesis and Characterization of New Biodegradable Injectable Thermosensitive Smart Hydrogels for 5-Fluorouracil Delivery.

In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) and zirconium(IV) acetylacetonate (Zr(acac)4), as co-initiator and catalyst, respectively. The structure, molecular weight (Mn) and molecular weight distribution (Đ) of the synthesized materials was studied in detail using nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the optimal synthesis conditions were determined. The structure corresponded well to the theoretical assumptions. The produced hydrogels demonstrated a sharp sol–gel transition at temperature close to physiological value, forming a stable gel with good mechanical properties at 37 °C. The kinetics and mechanism of in vitro 5-FU release were characterized by zero order, first order, Higuchi and Korsmeyer–Peppas mathematical models. The obtained results indicate good release control; the kinetics were generally defined as first order according to the predominant diffusion mechanism; and the total drug release time was approximately 12 h. The copolymers were considered to be biodegradable and non-toxic; the resulting hydrogels appear to be promising as short-term LDDSs, potentially useful in antitumor therapy.

Drug-release dynamics and antibacterial activities of chitosan/cefazolin coatings on Ti implants

Chitosan/drug (cefazolin) coatings were synthesized on alkali-treated Ti surfaces via electrophoretic deposition to improve the antibacterial activities and corrosion resistances of the surfaces. The coatings exhibited desirable adhesion to the alkali-treated Ti due to the penetration of chitosan and drug into the pores of the substrates. The chitosan were cationic molecules which carried drug and both of them migrated toward the cathode during electrophoretic deposition. At a low potential, the drug dissolved in the chitosan film, whereas at a high potential, the drug aggregated into sheets on the surface of chitosan. The high potential provided the coating with high drug loading and releasing capacity. The total drug release of chitosan/drug coatings with 4.3 and 6.9 μm thickness in Hank's balanced salt solution (HBSS) was about 3 and more than 14 days, respectively. The coatings exhibited increased corrosion resistance than the Ti in HBSS evaluated via potentiostat. Additionally, the coating with high drug loading demonstrated approximate 100% antibacterial activities against Escherichia coli; thus, the proposed coatings can be used as promising Ti coatings to limit bacterial adhesion and proliferation.

Combined Self-Nanoemulsifying and Solid Dispersion Systems Showed Enhanced Cinnarizine Release in Hypochlorhydria/Achlorhydria Dissolution Model.

The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release.