Zero-order Drug Release Research Articles

Lornoxicam controlled release transdermal gel patch: Design, characterization and optimization using co-solvents as penetration enhancers.

The aim of the current study was to develop membrane-based transdermal patches of lornoxicam gel using oleic acid (OA)and propylene glycol (PG) as penetration enhancers to improve drug delivery across the skin and to evaluate in vivo analgesic and anti-inflammatory activity. For this purpose, nine formulations were developed in accordance with 32 factorial design using Design Expert® 11. The concentration of propylene glycol (X1) and oleic acid (X2) were selected as independent variable whereas Q10 (Y1), flux (Y2) and lag time (Y3) were considered as the response variables. The impact of drug loading, surface area, gel concentration, membrane variation and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction, analgesic activity and anti-inflammatory action of the optimized patch were also determined in Albino Wistar rats. Stability studies were performed for three months at three different temperature conditions. The result suggests that a membrane-based system with controlled zero-order drug release of 95.8 ± 1.121% for 10 h exhibiting flux of 126.51±1.19 μg/cm2/h and lag time of 0.908 ±0.57h was optimized with the desired analgesic and anti-inflammatory effect can be obtained by using propylene glycol and oleic acid co-solvents as a penetration enhancer. The patch was also found stable at 4˚C for a period of 6.44 months. Formulation F9 comprising of 10% PG and 3% OA was selected as an optimized formulation. The study demonstrates that the fabricated transdermal system of lornoxicam can deliver the drug through the skin in a controlled manner with desired analgesic and anti-inflammatory activity and can be considered as a suitable alternative of the oral route.

Ethylcellulose-based drug nano depots fabricated using a modified triaxial electrospinning

New strategies based on advanced technologies are highly desired for expanding the applications of biological macromolecules in the applied scientific fields. In the present study, a new kind of core-shell nano depots were designed, in which the shell section was a drug-polymer composite and the core section was a drug reservoir. With ethyl cellulose and ketoprofen as a filament-forming polymeric matrix and a model drug, respectively, a triaxial electrospinning apparatus was developed to conduct both coaxial and triaxial processes, by which monolithic nanofibers F1 and core-shell nano depots F2 were successfully prepared. Although both of them had the same double components, their different nanostructures generated considerable differences in providing drug sustained release profiles. The core-shell nanofiber depots F2 were able to provide a better zero-order drug release profile: no initial burst release, smooth sustained release effect, and smaller tailing-off release for a nice zero-order drug release kinetics. The release percentage (Q) can be linearly manipulated through the release time (t) according to the equation Q2 = 9.40 + 4.74 t (R = 0.9936), providing opportunity for precise administration. The developed strategy and advanced electrospinning technique exhibit a new way for constructing process-structure-performance relationships at nano scale and for expanding the potential applications of biological macromolecules in the applied fields.

Citric acid crosslinking of mucilage from Cydonia oblonga engenders a superabsorbent, pH-sensitive and biocompatible polysaccharide offering on-off swelling and zero-order drug release

Present research demonstrated the crosslinking of Cydonia oblonga seeds hydrogel using citric acid (CA) and evaluated its stimuli-responsive swelling properties at different biomimetic pH, swelling/deswelling behavior against different fluids and sustained release potential in orally administered tablet formulation. Cross-linked C. oblonga hydrogel (CL-COH) was synthesized using four concentrations of CA, i.e., 1.25%, 2.5%, 5% and 10% and characterized through Fourier transform infrared (FTIR) spectroscopic analysis. CL-COH exhibited high swelling capacity at pH 6.8, 7.4 and in deionized water whereas, insignificant swelling was observed at pH 1.2. Swelling/deswelling response of CL-COH (2.5% CA) at pH 7.4 and 1.2, in deionized water and ethanol, and deionized water and normal saline were remarkable and reproducible results were obtained even after four cycles. Scanning electron microscopy (SEM) images of CL-COH indicated evenly distributed web of interconnected macro-pores. CL-COH was used as a pH-sensitive sustained release material for the preparation of oral tablet formulation of levosulpiride. In vitro drug release study revealed that the drug release followed zero-order kinetics and drug release mechanism was found as a super case II transport. Non-thrombogenic and non-hemolytic potential of CL-COH was ascertained through haemocompatibility studies. Therefore, CL-COH can be a versatile stimuli-responsive and biocompatible polysaccharide-based material for zero-order sustained release of drugs.

Study of Drug Release Kinetics from Sustained Release Matrix Tablets of Acyclovir using Natural Polymer Obtained from Colocasia Esculenta

Sustained-release (SR) matrix tablets of Acyclovir and polysaccharide isolated from corms of Colocasia esculenta, at different drug to polymer ratios, were prepared by using wet granulation method. The formulated tablets were also characterized by physical and chemical parameters and results were found in acceptable limits. The investigation focuses on the influence of the proportion of the matrix material on the mechanism and the release rate of the drug from the tablets. In vitro drug release appears to occur both by diffusion and a swelling-controlled mechanism, indicates the drug release from the tablet was non-Fickian super case II transport. The drug release data fit well to the Zero-order drug release Model and the Korsmeyer equation.

Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency.

Efficient encapsulation of hydrophilic drugs was substantially challenging when using emulsion solvent evaporation approach. The aim of present study was to design palonosetron hydrochloride-loaded PLGA microspheres (Pal-MS) with high encapsulation efficiency (EE) to sustain drug release for over several days. Pal-MS were prepared using emulsion-solvent evaporation method. Results showed that the pH of external phase could significantly affect the EE and the drug release rate of Pal-MS. By increasing the pH of external phase from 5.0 to 10.0, EE of Pal-MS increased from 55.64% to 94.33%. When the pH of external phase was 7.0, an ideal Pal-MS with EE of 86.51% and a zero-order drug release profile was obtained. The improved EE and drug release performance was proved to be associated with possible PLGA degradation, enhanced drug-PLGA interaction and reduced drug diffusion from organic phase to aqueous phase. After subcutaneous injection, such Pal-MS showed more steady drug plasma concentration (0.207-1.238ng/ml) over the entire 6-day in comparison with those of multiple-day-dosing intravenous palonosetron hydrochloride solution. It was concluded that Pal-MS were successfully designed by the adjustment of the pH of external phase and could be promising for preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV).

Citric acid cross-linked glucuronoxylans: A pH-sensitive polysaccharide material for responsive swelling-deswelling vs various biomimetic stimuli and zero-order drug release

Herein, we report on the cross-linking of a glucuronoxylan isolated from Mimosa pudica (MP) seed and its stimuli (biomimetic) responsive properties, i.e., pH, saline and solvent responsive swelling-deswelling. Cross-linked MP hydrogel (CL-MPH) was prepared by esterification of MPH using citric acid (CA) as a cross-linking agent (CLA). Three products of different cross-linking degree were synthesized with different concentrations of CA and characterized by FTIR spectroscopic analysis. CL-MPH (with 5% CA) showed high swelling at pH 6.8, 7.4 and in deionized water while negligible swelling was observed in pH 1.2. This CL-MPH sample exhibited swelling-deswelling (on-off switching) behavior in water to ethanol, water to saline (0.9% NaCl) and basic (pH 7.4) to acidic (pH 1.2) buffer, respectively. Scanning electron microscope (SEM) analysis revealed the presence of interconnected macro-pores in CL-MPH. Tablets prepared with CL-MPH and diclofenac sodium were evaluated for sustained release potential of CL-MPH. Drug release kinetics and release mechanism followed zero-order and non-Fickian diffusion, respectively. Haemocompatibility studies revealed the non-thrombogenic and non-haemolytic potential of CL-MPH. Due to these attributes of CL-MPH; it can find its applications as a pH-sensitive smart biomaterial for targeted/controlled/sustained drug delivery systems.

Soft implantable device with drug-diffusion channels for the controlled release of diclofenac

We propose the use of an implantable device with multiple embedded drug diffusion channels, each of which is connected to a drug reservoir, for the controlled release of diclofenac. To minimize the size of the incision needed during device implantation, the device used herein was made of the soft biocompatible material polydimethylsiloxane (PDMS), thereby allowing for folding during device implantation. We aimed to achieve a profile of diclofenac release that was reproducible even after folding, and thus the channel was filled with cross-linked gelatin, which could be swollen via the infiltration of a bodily fluid to compensate for any possible defects formed during folding. We first assessed the use of individual channels of varying lengths of 1–12 mm, and the onset time and average rate varied from 1 to 14 days and from 0.31–4.3%/day, respectively. According to these results, we prepared a device with multiple integrated pairs of drug reservoirs and channels of different lengths (i.e., the SDD_I), in which the channel combination was selected to achieve the long-term, zero-order release of the largest amount of drug. Thus, the SDD_I used herein exhibited almost zero-order drug release for 55 days at a release rate of 1.19%/day (179.8 μg/day), which did not vary even after the device was folded multiple times due to the presence of gelatin in the channel. When tested in living rats, the SDD_I device could be folded and inserted subcutaneously through an incision less than half the size of that needed for the implantation of the unfolded, intact SDD_I. For both the unfolded and folded SDD_I devices, the drug concentration in blood was observed to be maintained within a similar range due to the almost zero-order, reproducible release of diclofenac.

Three-dimensional (3D) printed tablets using ethyl cellulose and hydroxypropyl cellulose to achieve zero order sustained release profile

The main objective of this study was to investigate the potential of coupling hot-melt extrusion (HME) and 3D printing in order to design drug containing matrix tablets for the purpose of achieving zero order release. The effect of the blend ratio of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC), carbamazepine (CBZ) as a model drug and triethyl citrate (TEC) on the mechanical and printability properties of extruded filaments was investigated. Filament formulation containing CBZ, EC and HPC (3, 64.7 and 32.3% w/w, respectively) and 20% w/w of TEC (by weight on the dry powder) showed optimum mechanical and printability properties and subsequently was printed into tablets (370 mg, 13 mm diameter, 3.5 mm thickness, cylinder-shaped) at 187 °C. The printed tablets showed good uniformity in drug content and appropriate mechanical properties. The optimum filament showed first order drug release pattern, while the 3D printed tablets showed zero-order drug release and slower drug release rate than the optimum filament. Overall, we have demonstrated that zero order release tablets can be prepared from a 2:1 ratio of EC to HPC, by combination of HME and 3D printing technologies with the capability of reducing dose frequency and adverse effects of drugs.

Determinants of zero-order release kinetics from acetaminophen-layered Suglet® pellets, Wurster-coated with plasticized Aquacoat® ECD (ethyl cellulose dispersion).

The potential for zero-order drug-release was evaluated for ethyl cellulose (EC) coated, acetaminophen-layered sugar pellets (Suglets®) of mesh size 18/20 (850-1000μm). To determine optimal plasticizer/pore-former concentrations for EC films, solvent-cast Aquacoat® ECD (ethyl cellulose dispersion) films were prepared with 0-50% w/w ratios of two triethyl citrate (TEC) or triacetin (TA). Characterization studies showed that films with excipient concentrations ≥20% were homogenous, mechanically strong at room temperature (Young's modulus of 25-35MPa), and have a glass transition (Tg) in the range of 20-45°C. Based on these results, a working range of 20-50% weight concentrations was selected for drug release studies. Suglets® were layered with acetaminophen (APAP) using Wurster Glatt GPCG-3 to yield roughly 10% w/w coating (controls). The Controls were coated using the same Wurster process with Aquacoat® ECD containing 20-50% w/w of TEC or TA. Samples were removed periodically at 3-11% weight gain, to evaluate impact of weight gain, and consequently film-formation, on drug release. Dissolution was monitored over a period of 12h in a media consisting of simulated gastric fluid (first two hours), followed by simulated intestinal fluid. The controls showed near 100% release within the first 30min, indicating the value of EC-coating to achieve controlled release. Dissolution release profiles showed that TEC is more effective than TA as a plasticizer and pore-former, as linear profiles were apparent at lower concentrations and % weight gain. For a quantitative evaluation of these results, linear regression was fitted to all cumulative release profiles, and R-squared values examined as a function of excipient concentration and % weight gain. The corresponding response surface plots and the second order regression were shown to aid in optimization. The design space for zero-order release was represented as contour plots between excipient concentration and % weight gain.

Customized Novel Design of 3D Printed Pregabalin Tablets for Intra-Gastric Floating and Controlled Release Using Fused Deposition Modeling.

Three-dimensional (3D) printing has been recently employed in the design and formulation of various dosage forms with the aim of on-demand manufacturing and personalized medicine. In this study, we formulated a floating sustained release system using fused deposition modeling (FDM). Filaments were prepared using hypromellose acetate succinate (HPMCAS), polyethylene glycol (PEG 400) and pregabalin as the active ingredient. Cylindrical tablets with infill percentages of 25%, 50% and 75% were designed and printed with the FDM printer. An optimized formulation (F6) was designed with a closed bottom layer and a partially opened top layer. Filaments and tablets were characterized by means of fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and thermogravimetric analysis (TGA). The results show that the processing condition did not have a significant effect on the stability of the drug and the crystallinity of the drug remained even after printing. A dissolution study revealed that drug release is faster in an open system with low infill percentage compared to closed systems and open systems with a high infill ratio. The optimized formulation (F6) with partially opened top layer showed zero-order drug release. The results show that FDM printing is suitable for the formulation of floating dosage form with the desired drug release profile.

FORMULATION AND EVALUATION OF GLICLAZIDE NANOSPONGES

Objective: The objective of the present study was to develop and characterize an optimal stable nanosponges of Gliclazide (GLZ) by using the emulsion solvent diffusion method and aimed to increase its bioavailability and release the drug in sustained and controlled manner.
 Methods: The GLZ nanosponge was prepared by emulsion solvent diffusion method using different drug-polymer ratios (1:1 to 1:5) Eudragit S100 is used as a polymer. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) estimated the compatibility of GLZ with polymer. All formulations evaluated for production yield, entrapment efficiency, in vitro drug release, scanning electron microscopy (SEM) and stability studies.
 Results: The DSC and FTIR Studies revealed that no interaction between drug and polymer. The Production yield of all batches in the range of 73.8±0.30 to 85.6±0.32. Batch F3 showed the highest production yield, the entrapment efficiency of batch F3 70.6±0.77. The average particle size ranges from 303±2.36 to 680±2.50 nm. By the end of 10th hour F3 formulation shown highest drug release was found to be 94.40±1.12%. The release kinetics of the optimized formulation shows zero-order drug release. The stability study indicates no significant change in the in vitro dissolution profile of optimized formulation.
 Conclusion: The results of various evaluation parameters, revealed that GLZ nanosponges would be possible alternative delivery systems to conventional formulation to improve its bioavailability, the emulsion solvent diffusion method is best method for preparation of nanosponges and release the drug in sustained and controlled manner.

The Effect of Polydimethylsiloxane-Ethylcellulose Coating Blends on the Surface Characterization and Drug Release of Ciprofloxacin-Loaded Mesoporous Silica.

In this study, we obtained novel solid films composed of ciprofloxacin-loaded mesoporous silica materials (CIP-loaded MCM-41) and polymer coating blends. Polymer coating blends were composed of ethylcellulose (EC) with various levels of polydimethylsiloxane (PDMS, 0, 1, 2% (v/v)). The solid films were prepared via the solvent-evaporation molding method and characterized by using scanning electron microscopy (SEM), optical profilometry, and wettability analyses. The solid-state of CIP present in the solid films was studied using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The release profiles of CIP were examined as a function of PDMS content in solid films. The surface morphology analysis of solid films indicated the progressive increase in surface heterogeneity and roughness with increasing PDMS content. The contact angle study confirmed the hydrophobicity of all solid films and significant impact of both PDMS and CIP-loaded MCM-41 on surface wettability. DSC and XRD analysis confirmed the presence of amorphous/semi-crystalline CIP in solid films. The Fickian diffusion-controlled drug release was observed for the CIP-loaded MCM-41 coated with PDMS-free polymer blend, whereas zero-order drug release was noticed for the CIP-loaded MCM-41 coated with polymer blends enriched with PDMS. Both the release rate and initial burst of CIP decreased with increasing PDMS content.

Fabrication of Zero-Order Sustained-Release Floating Tablets via Fused Depositing Modeling 3D Printer.

A three-dimensional (3D) printer is a powerful tool that can be used to enhance personalized medicine. A fused deposition modeling (FDM) 3D printer can fabricate 3D objects with different internal structures that provides the opportunity to introduce one or more specific functionalities. In this study, zero-order sustained-release floating tablet was fabricated using FDM 3D printer. Filaments comprising poorly water-soluble weak base drug, itraconazole (ITZ) and polymers (hydroxypropyl cellulose and polyvinylpyrrolidone) were prepared, and tablets with a hollow structure and different outside shell thicknesses were fabricated. In the 3D printed tablets, ITZ existed as an amorphous state and its solubility improved markedly. As the outside shell thickness of the tablet increased, drug release was delayed and floating time was prolonged. In the tablets with 0.5 mm of the upper and bottom layer thickness and 1.5 mm of the side layer thickness, holes were not formed in the tablets during the dissolution test, and the tablets floated for a long period (540 min) and showed nearly zero-order drug release for 720 min. These findings may be useful for improving the bioavailability of several drugs by effective absorption from the upper small intestine, with floating gastric retention system.

Biocompatible Fe3+ and Ca2+ Dual Cross-Linked G-Quadruplex Hydrogels as Effective Drug Delivery System for pH-Responsive Sustained Zero-Order Release of Doxorubicin.

The ultimate aim in developing controlled drug delivery systems is to derive formulations to achieve drug release at a constant rate over a long duration. The drug release profile that follows zero-order kinetics is crucial for reduction in the drug administration frequency, reduced cytotoxicity, and improved convenience and compliance of patients. Designed drug delivery systems for achieving zero-order release are often complex, expensive, and difficult to manufacture. Herein, we demonstrate that a supramolecular hydrogel formed through the self-assembly of guanosine monophosphate (GMP) into highly ordered G-quadruplex structure and cross-linked through Fe3+ and Ca2+ ions exhibits potential for the pH-responsive controlled zero-order drug release of doxorubicin, a model chemotherapeutic drug. The fibril formation is initiated by the self-assembly of GMP into a quadruplex complex, which is cross-linked through the complexation of the phosphate groups with Fe(III) ions, resulting in a spontaneous hydrogel formation. The Ca2+ ions facilitate the improvement in the mechanical integrity of the fibril network in the Fe-GMP hydrogel via cross-linking of sugar moieties. The hydrogel showed a high loading capacity for drug molecules and a pH-responsive sustained zero-order drug release over several days owing to the lowered degradability of the cross-linked hydrogel in acidic buffer stimulant. In vitro drug-release studies further established a controlled pH-triggered drug release profile. The Ca2+ cross-linking of the Fe-GMP hydrogel also resulted in significant enhancement in the biocompatibility of the drug delivery system. The fabrication of biocompatible, low-cost, and efficient Ca2+ cross-linked metal-organic hydrogels may present promising applications in biological fields.

Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology

Three dimensional printing technologies are widely used in medical applications, reflecting the ease of customization and personalization. Hence, applications of 3D printing in pharmaceutical manufacturing may provide variety and complexity of pharmaceutical dosage forms that conventional methods do not. 3D printing can be used to produce individualized drug and dosage forms for future therapeutic application. Herein, we developed a pharmaceutical formulation in the form of a floating controlled drug-release tablet loaded with a metronidazole core using 3D printing. The floating shell or tablet housing was prepared from polyvinylalcohol. Initially, shapes of tablet floating housings were designed and printed in cylinder, sphere and cone shapes. Metronidazole tablet cores were then prepared by direct compression and were assembled into the printed tablet housing. We then examined the effects of shapes of the floating tablet housing, pole sizes for drug release and air volumes for floating. Cylindrical floating tablet housings floated stably at the surface of water. These tablets also floated immediately and for more than 4 h, and drug release was more than 88% after 8 h. Floating tablets with a pore sizes of 2.0 mm and air volumes of 132 mm3 provided zero-order drug release in kinetic investigations, with an r2 value of 0.9661.

Intra-articular Treatment of Osteoarthritis with Diclofenac-Conjugated Polymer Reduces Inflammation and Pain.

The most common treatment for osteoarthritis is daily oral administration of a nonsteroidal anti-inflammatory drug such as diclofenac. This daily dosage regime is often associated with severe side effects. In this study, we explored the potential of utilizing a high molecular weight cross-linked polyurethane polymer covalently linked to diclofenac (C-DCF-PU) for intra-articular administration. We aim to exploit the advantages of local drug delivery by developing an implant with improved efficacy and reduced side effects. The polymer was synthesized from a diclofenac-functionalized monomer unit in a simple one-pot reaction, followed by cross-linking. In vitro drug release studies showed zero-order drug release for 4 days, followed by a gradual decline in drug release rate until diclofenac was depleted after 15 days. The cross-linked polymer was triturated to yield an injectable microgel formulation for administration. Whole animal fluorescence imaging of the rhodamine-labeled C-DCF-RH-PU showed good retention of the polymer in the knee joints of healthy rats, with approximately 30% of the injected dose still present 2 weeks post intra-articular administration. In a reactivation arthritis animal model, the C-DCF-RH-PU formulation reduced pain and significantly reduced inflammation after a short lag phase, showing that this drug delivery system warrants further development for long-term treatment of osteoarthritis with the benefit of reduced side effects.

COMPARATIVE STUDY OF SPAN 40 AND SPAN 60 BASED SOY-GELS FOR TOPICAL DRUG DELIVERY

Objective: Hydrogels or emulgels are recommended for topical application to elicit a local effect. However, they suffer from stability problems. The present study deals with the formulation and comparison of thermally stable soybean oil-based novel topical organogels (soy-gels) using two different gelators (Span 40 and Span 60) for controlled drug delivery.
 Methods: Soy-gels (8 batches) were developed with Span 40 and Span 60 by solid fiber mechanism and characterized for viscosity, gelation kinetics behavior, gel-sol transition parameters, drug content, in vitro drug release pattern, and changes occurring during accelerated thermal stability studies.
 Results: Fourier transformed infrared spectroscopic confirmed the compatibility among the organogel components and paracetamol. The formulations exhibited skin and hemocompatibility. The viscosity of Span 60 based soy-gels was found to be approximately 10 times higher than those of Span 40 based formulations. In comparison to Span 40, Span 60 induced faster gelation (3–6 min) of soybean oil at lower concentration (16% w/v) forming less flexible but thermally more stable soy-gels demonstrating higher Tg values. Higher flexibility and lower viscosity accounted for improved drug diffusion (both Fickian and non-Fickian) from Span 40 gels of varying concentrations in pH 5.8. However, zero-order drug release was observed in organogel with 18% w/v Span 40 only and all Span 60-based formulations except the one with 22% w/v Span 60. Non-Fickian drug diffusion occurred from Span 60 based soy-gels. A gradual increase in gelation time was observed until five cycles of freeze-thaw.
 Conclusion: Therefore, the choice of organogelator governs the rheological, thermal, and drug diffusion properties of soy-gels intended for topical application.

Theoretical study of diffusional release of a dispersed solute from cylindrical polymeric matrix: A novel configuration for providing zero-order release profile

• A novel design for polymeric matrixes , containing dispersed solute, has been suggested for providing zero-order release. • Mathematical modeling and simulation have been carried out to evaluate the performance of the suggested system. • The effect of coating degradation rate on the release profile has been assessed through the mathematical simulation. • The effect of solute loading level on the release profile has been assessed through the mathematical simulation. • The suggested system is able to eliminate burst release at initial time and provide approximate zero-order behavior. In the context of controlled release drug delivery approaches, the systems providing zero-order release kinetics have special advantages. Through employing these systems, drug concentration could be maintained within the therapeutic window over release time; thus maximum effectiveness alongside minimized side effects of the drug are achieved. However, obtaining zero-order drug release is extremely challenging. One of the main obstacles is the fact that implemented devices should be designed to overcome the decreasing mass transfer driving force, especially, in polymeric systems in which diffusion mechanism is dominant. In this study, we developed a new configuration of a polymeric matrix containing dispersed solute which provides sustained zero-order release. A combination of two innovative approaches including separating baffles and a two-layer coating was proposed to be incorporated into the conventional cylindrical polymeric matrix to induce zero-order release behavior. Then, an approximate mathematical model was developed to investigate the performance of the system under different conditions. The simulated results showed the potential of proposed configuration to be used as a carrier for sustained zero-order release.

Tunable drug release from blend poly(vinyl pyrrolidone)-ethyl cellulose nanofibers

The management of pain and inflammation arising from wounds is essential in obtaining effective healing rates. The application of a wound dressing loaded with an anti-inflammatory drug would enable both issues to be ameliorated, and the aim of this work was to fabricate such a dressing by electrospinning. Fibers comprising ethyl cellulose (EC) and poly(vinyl pyrrolidone) (PVP) loaded with naproxen (Nap) were developed to be used in the early stages of wound care. A family of PVP/EC/Nap systems was prepared by varying the PVP: EC ratio. In all cases, the products of electrospinning comprise non-woven mats of fibers which generally have smooth and cylindrical morphologies. The formulations exist as amorphous solid dispersions, and there appear to be intermolecular interactions between the three components. Adjusting the polymer ratios results in tunable drug release, and formulations have been produced which give zero-order drug release over 20 and 80 h. The fiber mats generated in this work thus have great potential to be used as dressings for the treatment of wound pain and inflammation.

In Vitro and In Silico Analyses of Nicotine Release from a Gelisphere-Loaded Compressed Polymeric Matrix for Potential Parkinson's Disease Interventions.

This study aimed to develop a prolonged-release device for the potential site-specific delivery of a neuroprotective agent (nicotine). The device was formulated as a novel reinforced crosslinked composite polymeric system with the potential for intrastriatal implantation in Parkinson’s disease interventions. Polymers with biocompatible and bioerodible characteristics were selected to incorporate nicotine within electrolyte-crosslinked alginate-hydroxyethylcellulose gelispheres compressed within a release rate-modulating external polymeric matrix, comprising either hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), or poly(lactic-co-glycolic) acid (PLGA) to prolong nicotine release. The degradation and erosion studies showed that the produced device had desirable robustness with the essential attributes for entrapping drug molecules and retarding their release. Zero-order drug release was observed over 50 days from the device comprising PLGA as the external matrix. Furthermore, the alginate-nicotine interaction, the effects of crosslinking on the alginate-hydroxyethycellulose (HEC) blend, and the effects of blending PLGA, HPMC, and PEO on device performance were mechanistically elucidated using molecular modelling simulations of the 3D structure of the respective molecular complexes to predict the molecular interactions and possible geometrical orientation of the polymer morphologies affecting the geometrical preferences. The compressed polymeric matrices successfully retarded the release of nicotine over several days. PLGA matrices offered minimal rates of matrix degradation and successfully retarded nicotine release, leading to the achieved zero-order release for 50 days following exposure to simulated cerebrospinal fluid (CSF).