Initial Drug Release Research Articles

The preparation of melt electrospun fiber containing tandospirone for drug sustained release

AbstractElectrospun fibers membrane is considered an efficient drug carrier for transdermal drug delivery due to its breathability and high drug loading percentage, compared with coating film. However, pollution and safety risk caused by the use of organic solvents during the solution electrospinning process limit its industrialization and direct application in the biomedical field. Herein, a fiber membrane containing tandospirone was prepared using the melt electrospinning process and to be used for sustained drug release. The process of fiber preparation is an eco‐friendly and safe process due to the characteristics of solvent‐free. The in vitro drug release results showed that the fiber membranes containing tandospirone had slower initial drug release and higher end drug release compared with coating film containing tandospirone. The sustained‐release property can be attributed to the crystalline structure of fibers and the higher‐end drug release can be attributed to the spatial packing structures in the fiber membrane. The large pores generated by the stack structure of the large fiber in the fiber membrane leads to low gas resistance (10.7 Pa), which is much lower than that of the coating film (511.2 Pa). Overall, this study presents a green and safe preparation method of fiber membrane containing tandospirone, providing an effective and adjunctive treatments for mental disorders.Highlights The tandospirone‐loaded fiber patch was prepared using an eco‐friendly method. Burst release inhibition and higher final release of tandospirone in fibers. The fiber patch provided excellent breathability compared to coating patch. Fibers with higher crystallinity showed better controlled release.

Abstract 2123: Validation of novel histone deacetylases (HDAC) specific nanoparticles using HDACs overexpressed human embryonic kidney cells

Abstract Introduction: Histone deacetylase (HDAC) is a major enzyme system that is upregulated in numerous disease conditions including cancer. Harnessing the upregulation of HDAC can be a viable tool to design targeted therapy for these diseases. Nanoparticle technology has emerged as a powerful workhorse to suppress the survival of diseased cells selectively. As such, we aim to design a nanoscale, drug delivery platform that responds to HDAC enzymes to initiate drug release. In this poster, we show the pharmacological evidence that HDAC-sensitive nanoparticles are interacting with HDAC enzymes in vitro in time and concentration dependent pattern. Methods: We synthesized HDAC-responsive nanoparticles via developing a block copolymer composed of a poly (ethylene glycol) block and a poly (L-acetylated lysine) block. Abbreviated as PEG-acPLK, these copolymers self-assemble as nanoparticles with negatively charged surface. Using in vitro culture of HEK 293 cells, we showed that the formed nanoparticles interact and interfere with HDAC enzymes. Cells were grown to 80-90% confluency in DMEM media w/10% FBS prior to experiments. HEK-293 cells were overexpressed with HDAC 7 & HDAC 8 using Lentiviral vectors. Western blot was done to prove the successful overexpression of the HEK cells. Cytotoxicity assay was done by MTT to analyze the efficacy of HDAC specific nanoparticle on control and overexpressed HEK-293 cells. Results: Our work showed that, PEG-acPLK systems form nanoparticles with a hydrodynamic diameter (RH) of 120-150 nm. The particles were negatively charged on their surface, as such did not produce any non-specific toxicity to cells, such as damage of cell membranes. HEK-293 cells were infected with lentivirus vectors for HDAC 7 and HDAC 8. The medium was changed 8 h after infection. Forty-eight hours after infection, the positive cells were selected with 5 µg/mL puromycin. The lentivirus stable transformants of HEK-293 cells were collected and significant overexpression were confirmed by western blot. For the cytotoxicity study, control and overexpressed cells were treated with HDAC-nanoparticle and PEG-acPLKC (5 µg/mL to 70 µg/mL) for 24hrs. Both the HDAC-nanoparticle and PEG-acPLC (free form) showed more than 60% of toxicity at the concentration of 20 µg/mL. Whereas the HDAC 7 and 8 overexpressed HEK-293 cells did not showed any effects with nanoparticle and Ae-peg-PLKC, suggesting compensating effect due to highly available HDAC system in place and confirm the effectiveness of the HDAC nanoparticle. Summary and Conclusion: Overall, these results showed that HDAC specific nanoparticle exhibited effects in HEK-293 HDACs overexpressed cells. Further molecular mechanistic studies will help to delineate how the HDAC-responsive particles can be used for drug delivery. Citation Format: Sahil Lohana, Yogaraj Ramakrishnan, Premanand Balraj, Md Rakib Hasan Khan, Mallik Sanku, Venkatachalem Sathish, Mohiuddin Quadir. Validation of novel histone deacetylases (HDAC) specific nanoparticles using HDACs overexpressed human embryonic kidney cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2123.

Electrospun photothermally active graphene-based nanofibers with a Retro-Diels-Alder reaction to initiate drug release

Externally controlled local drug release systems have garnered significant interest, with stimuli-responsive electrospun nanofibers emerging as a prominent platform for local drug delivery. Their advantages, such as a high surface area and facile production have made them appealing materials for various biomedical applications. While nanofiber scaffolds have been widely used for drug release through physical entrapment, control over the passive release and precise dosage regulation remains challenging. To overcome these limitations, in this study, maleimide-modified functional molecules were covalently conjugated to reduced graphene oxide-containing nanofiber scaffolds (average diameter 475 ± 94 nm) fabricated using furan-containing copolymers. The Diels-Alder cycloaddition at ambient temperature conjugates the molecules of interest, whereas the thermally promoted retro Diels-Alder cycloreversion reaction releases them. Photothermal heating using near-infrared light at 980 nm facilitated control over the drug release, and switching the irradiation on and off allows on-demand release. One can envision that these photothermally active nanofiber mats could enable on-demand drug delivery of a variety of active therapeutic agents for localized delivery.

Development of Ethylcellulose Microparticles for Taste Masking of Fexofenadine.

For taste masking of fexofenadine hydrochloride (FXD), ethylcellulose (EC) microparticles with FXD were developed. The amounts of EC, Tween 80, and polyvinyl alcohol (PVA) in the composition had little effect on initial drug release properties. Based on the results of the drug recovery and the drug release properties, FXD(EC200) was the optimal FXD microparticle formulation. From the results of Fourier transform infrared spectroscopy spectra and X-ray diffraction patterns of FXD(EC200), FXD amorphization in the microparticles and interaction between FXD and other components were suggested, and the formation of a solid dispersion of FXD was suggested. Because the possibility of the complex of PVA and FXD on the particle surface was suggested, sodium lauryl sulfate (SLS) was added to the composition. The initial drug release from FXD microparticles with SLS was further suppressed compared with FXD(EC200). From these results, FXD microparticles with SLS can be prepared as a controlled-release formulation and are expected to be useful for masking the bitter tasting particulates.

Optimization of variables and assessment of in-vitro and in-vivo antihyperlipidemic activity of Eudragit RS nanoparticles containing simvastatin

Simvastatin, a BCS class II drug, is associated with poor aqueous solubility, first-pass metabolism and short half-life. In the present work, nanoparticles were prepared and evaluated. Optimization of formulation and process parameters was done through the use of independent and dependent variables. Preliminary studies were done to determine suitable range of the concentration of Eudragit polymer (10%–30%) and the ratio of drug to polymer (1:1 to 1:5) for the formation of nanoparticles by emulsification and a solvent evaporation technique. Results revealed that the mean size of nanoparticles was affected by stirring speed from 5000 RPM, 8000 RPM, and 12000 RPM. The results of increase in association efficiency and percent yield with increase in amount of drug from 100 mg, 150 mg, and 200 mg in selected range were observed. In-vitro release studies showed that two formulations possess highest initial burst and slow sustained drug release. There was 2.93-fold decrease in total cholesterol and 3.27-fold increases in triglyceride level during in-vivo study.

Zero-order Release of Metformin in Polyacrylamide Hydrogel

Water-soluble polymers with a three-dimensional crosslinked network structure, known as a hydrogel, has widespread applications in clinical and experimental medicine as drug carriers. Upon entering the targeted area for treatment, hydrogel loaded with drugs releases them through both diffusion and self-degradation mechanisms. In this study, the drug release process in polyacrylamide hydrogel uniformly loaded with metformin hydrochloride is investigated. To achieve a uniform drug release rate from the hydrogel, we establish a statistical model of drug release from polyacrylamide hydrogel using response surface methodology based on experimental design technique. The established statistical model can predict drug release behavior at a low cost within the design domain. The relationship between initial drug concentration and drug release rate in metformin-loaded polyacrylamide hydrogel has been investigated. A zero-order drug release effect in hydrogels is achieved through an optimized design of the initial distribution of drug concentration of a five-layered drug-containing hydrogel. This study has significant implications for the realization of drug molecule transport and sustained release in vivo.

Formulation of chitosan based lipid polymer hybrid nanocarrier system for oral delivery of tamoxifen citrate: Toxicological and hemocompatibility evaluation

The objective of the current work was to develop chitosan based lipid nanocarriers for the oral controlled release of tamoxifen citrate (TC). The ionic gelation method was used to develop various formulations with altered ratios of polymer, lipid, and emulsifier. The developed lipid hybrid nanoparticles (LHNPs) were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, SEM, DSC, FTIR, PXRD, in vitro release studies, stability studies, kinetic modeling, toxicity studies, and hemocompatibility assay. Particle size and entrapment efficiency of the developed formulations varied between 138.2 ± 4.2 nm to 281.8 ± 63.1 nm and 70.94 ± 0.29 % to 82.23 ± 0.02 %, respectively. The polydispersity index and zeta potential ranged from 0.199 ± 0.03 to 0.555 ± 0.01 and 17.9 ± 0.62 to 32.3 ± 0.36, respectively. Nano-sized, spherical in shape surfaces of developed particles were depicted by SEM. While removal of TC melting endotherm revealed by DSC analysis, suggested good thermal stability of LHNPs. FTIR verified that the components of the formulation do not interact chemically. PXRD depicted that the developed formulation has been successfully amorphized. In vitro release study revealed drug release, an initial burst drug release followed by the controlled release up to 72 h. Kinetic modeling exposed that all developed formulations showed a non-Fickian diffusion profile and were best fitted into Higuchi's square root and Korsmeyer-Peppas models. Toxicity investigations on female albino rabbits provided evidence for the compatibility and non-toxicity of developed particles with biological systems. Hemocompatibility assay showed that the developed system is compatible with blood and nontoxic. These investigations demonstrate the potential of developed LHNPs as a vehicle, aimed at controlled oral delivery of TC for better therapeutic applications in breast cancer.

Development and optimization of sustained release triptolide microspheres.

Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X1), PLGA concentration (X2), and theoretical drug content (X3) were selected as independent variables; and drug content (Y1), encapsulation efficiency (Y2), mean diameter (Y3) and the initial release during the first day (Y4) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future.

Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies.

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box-Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of -16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanoparticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ against tumor cells in vivo. In this study, CFZ-loaded tPNPs are stabilized by polycations which have varying pKa values and thus differently modulate nanoparticle stability in response to solution pH. Through polyion complexation, the polycations appeared to stabilize the core of tPNPs entrapping CFZ-cyclodextrin inclusion complexes while allowing for uniform particle size before and after freeze drying. Interestingly, CFZ-loaded tPNPs (CFZ/tPNPs) showed pH-dependent drug release kinetics, which accelerated CFZ release as solution acidity increased (pH < 6) without compromising particle stability at the physiological condition (pH 7.4). In vitro cytotoxicity and proteasome activity assays confirmed that tPNPs stabilized with cationic polymers improved bioactivity of CFZ against CFZ-resistant cancer cells, which would be greatly beneficial in combination with pH-dependent drug release for treatment of solid cancers with drug resistance and tumor microenvironment acidosis by using CFZ and other proteasome inhibitors.

Efficacy of co-loading Ag nanoparticles and metronidazole in PEG–gelatin-based sponges for the treatment of chronic wounds

Polymer-based sponges loaded with antibacterial agents are potential wound dressings ideal for treating bacteria-infected wounds. Gelatin/poly (ethylene glycol) (PEG) sponge-based wound dressings loaded with metronidazole and Ag nanoparticles with different degrees of cross-linking were prepared, and their capability to treat infected wounds in vitro was evaluated. The degree of cross-linking of the sponges varied, and the porosity of the sponges was in the range of 15.64–91.10%. The amount of gelatin used to prepare the sponges influenced the porosity of the sponges. The sponges displayed an initial burst drug release of metronidazole followed by a sustained release profile. The sponges exhibited considerable antibacterial activity against Gram-positive and Gram-negative bacteria. The % cell viability of the sponges was in the range of 71.17–86.10%, indicating distinguished biocompatibility. The in vitro experiment showed that the sponge loaded with metronidazole, SAM2%, displayed a significant reduction of 66.68% in the scratch area compared to the sponge loaded with a combination of silver nanoparticles and metronidazole with a closure rate of 46.61% at 96 h. The promising features of the sponges indicate that they are potential wound dressings for treating infected wounds.

Development of an anti-infective urinary catheter composed of polyvinyl alcohol/sodium alginate/methylcellulose/polyethylene glycol by using a pressure-assisted 3D-printing technique

Catheter-associated urinary tract infections (CAUTI) are a common complication associated with catheterization, leading to urosepsis, bacteriuria, and septicaemia. The present work focuses on 3D printing a urinary catheter with anti-infective properties using various concentrations of polyvinyl alcohol (PVA, e.g., 6–8 %), sodium alginate (NaAlg, e.g. 1–4 %), methylcellulose (MC, 5 %), polyethylene glycol (PEG, 5 %) impregnated with secnidazole, an antibiotic acting against Gram-negative bacteria. To produce suitable polymer ink for Pressure Assisted Microsyringe (PAM) 3D printing, the cross-linked between NaAlg and calcium chloride is necessary to prepare the catheter. The optimised catheter was found to have an outer diameter of 5 mm, an inner diameter of 3.5 mm, and a length of the catheter of 50 mm. The analysis by various methods confirms the successful incorporation of secnidazole in the 3D-printed catheter. A drug-loaded/coated catheter showed an initial drug release of 79 % following a sustained release to reach 100 % within 5 h. Weibull model fits well with the drug release data. The release models suggest the Quasi-Fickian diffusion mechanism from the system. Moreover, the secnidazole 3D printed catheter disrupted biofilms and suppressed all the Quorum sensing mediated virulence factors of two important keystone pathogens causing urinary tract infections.

Acriflavine-Functionalized Silica@Manganese Ferrite Nanostructures for Synergistic Radiation and Hypoxia Therapies.

Mesoporous and nonmesoporous SiO2@MnFe2O4 nanostructures were loaded with the hypoxia-inducible factor-1 inhibitor acriflavine for combined radiation and hypoxia therapies. The X-ray irradiation of the drug-loaded nanostructures not only triggered the release of the acriflavine inside the cells but also initiated an energy transfer from the nanostructures to surface-adsorbed oxygen to generate singlet oxygen. While the drug-loaded mesoporous nanostructures showed an initial drug release before the irradiation, the drug was primarily released upon X-ray radiation in the case of the nonmesoporous nanostructures. However, the drug loading capacity was less efficient for the nonmesoporous nanostructures. Both drug-loaded nanostructures proved to be very efficient in irradiated MCF-7 multicellular tumor spheroids. The damage of these nanostructures toward the nontumorigenic MCF-10A multicellular spheroids was very limited because of the small number of nanostructures that entered the MCF-10A spheroids, while similar concentrations of acriflavine without nanostructures were toxic for the MCF-10A spheroids.

Control of drug release kinetics from hot-melt extruded drug-loaded polycaprolactone matrices.

Sustained local delivery of meloxicam by polymeric structures is desirable for preventing subacute inflammation and biofilm formation following tissue incision or injury. Our previous study demonstrated that meloxicam release from hot-melt extruded (HME) poly(ε-caprolactone) (PCL) matrices could be controlled by adjusting the drug content. Increasing drug content accelerated the drug release as the initial drug release generated a pore network to facilitate subsequent drug dissolution and diffusion. In this study, high-resolution micro-computed tomography (HR μCT) and artificial intelligence (AI) image analysis were used to visualize the microstructure of matrices and simulate the drug release process. The image analysis indicated that meloxicam release from the PCL matrix was primarily driven by diffusion but limited by the amount of infiltrating fluid when drug content was low (i.e., the connectivity of the drug/pore network was poor). Since the drug content is not easy to change when a product has a fixed dose and dimension/geometry, we sought an alternative approach to control the meloxicam release from the PCL matrices. Here, magnesium hydroxide (Mg(OH)2) was employed as a solid porogen in the drug-PCL matrix so that Mg(OH)2 dissolved with time in the aqueous environment creating additional pore networks to facilitate local dissolution and diffusion of meloxicam. PCL matrices were produced with a fixed 30wt% meloxicam loading and variable Mg(OH)2 loadings from 20wt% to 50wt%. The meloxicam release increased in proportion to the Mg(OH)2 content, resulting in almost complete drug release in 14 d from the matrix with 50wt%Mg(OH)2. The porogen addition is a simple strategy to tune drug release kinetics, applicable to other drug-eluting matrices with similar constraints.

Development of a complex of doxorubicin with nanoparticles based on sodium alginate and viologen calix[4]resorcinol to increase selectivity of cytotoxic action

A biocompatible supramolecular system based on sodium alginate and viologen calix[4]resorcinol for encapsulation of doxorubicin hydrochloride (DOX) was obtained. Using a set of physicochemical methods, the polymer- macrocycle ratio was found, at which stable nanoparticles are formed, and their morphological characteristics were determined. It was shown that with an increase in the concentration of calix[4]resorcinol, the size of nanoparticles increases and the zeta potential changes from negative to positive values. It was established that the most optimal supramolecular system for DOX binding is a composition with a macrocycle-polymer ratio of 1:50, and a change in the ratio of components can initiate drug release. The effect of encapsulated DOX on the physicochemical and biological properties of the supramolecular system was shown.

Design and Optimization of Omeprazole-Curcumin-Loaded Hydrogel Beads Coated with Chitosan for Treating Peptic Ulcers.

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-β-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads to sustain their release and then coated with chitosan. Finally, we tested the anti-ulcerogenic impact of the best formula versus free OMP or OMP-only-loaded beads. The formulated spherical beads' diameter ranged from a minimum value of 1.5 ± 0.08 mm to 2.6 ± 0.24 mm; the swelling results ranged from 400.00 ± 8.5% to 800.00 ± 6.2%. The entrapment efficiency was in a range from 60.85 ± 1.01% to 87.44 ± 1.88%. The optimized formula (F8) showed a maximum EE% (87.44 ± 1.88%), swelling (800.00 ± 6.2%), and diameter in the range of 2.60 ± 0.24, with a desirability of 0.941. In the first hour following the administration of the free drug complex, 95% of OMP and 98% of CURC were released. This is unacceptable for medications that require a delayed release in the stomach. The initial drug release from hydrogel beads was 23.19% for CURC and 17.19% for OMP after 2 h and 73.09% for CURC and 58.26% for OMP after 12 h; however, after 24 h, 87.81% of CURC and 81.67% of OMP had been released. The OMP/CURC beads showed a more stable particle size (0.52 ± 0.01 mm) after 6 weeks. In conclusion, the OMP/CURC hydrogel beads give stronger anti-ulcer effectiveness compared to free OMP, CURC-only beads, and OMP-only-loaded beads, indicating a prospective application for managing peptic ulcers.

Formulation and Evaluation of Lisinopril Double Layer Tablet

Lisinopril is an antihypertensive drug that is primarily used in the treatment of hypertension, congestive heart failure, heart attacks and also in preventing renal and retinal complication of diabetes that acts by inhibiting angiotension converting enzyme (ACE). The present investigation deals with the formulation of lisinopril double layer tablet containing 100 mg fast release layer and 100 mg sustained release layer to be formulated using wet granulation method. Twelve formulations are prepared for bilayered tablets; 6 formulas for fast release layer study (FF1 to FF6) and another 6 formulas for the sustained release layer study. Friability of all formulation was less than 1%, which indicates the tablets had good mechanical resistance. Drug content was found to be uniform in all formulas. The tablet thickness was found to be 5.12 to 5.31 mm. Acceptable weight variation and content uniformity. Hardness was low for fast release lisinopril layer formulas FF1 to FF6, while it was high for formulas used to study the sustained release layer (SF1 to SF6). On the other hand disintegration time was short for formulas containing super disintegrant as crospovidone 15, and 10 seconds, croscarmelose 27, and 24 seconds and sodium starch glycolate 24, and 19 seconds and the shortest time for disintegration was for crospovidone containing formulas (FF1, and FF4); 15, and 10 seconds respectively for fast release layer study with no disintegration for the formulas used to study the sustained release of lisinopril. At the same time the release study for formulas containing crospovidone was within 20 minutes, while formulas containing HPMC K100 was 12 hours release. To be concluded that double layer tablets were attempted to be prepared for controlled drug delivery. The first layer of lisinopril provides the initial drug release while the second layer provides sustained release of lisinopril for increase patient compliance and decrease frequency of dosing for more control of hyper tension.

Control of API release with matrix polymorphism in tristearin microspheres

Glycerides are widely employed as solid matrices in a range of pharmaceutical intermediates and dosage forms. Diffusion-based mechanisms are responsible for drug release, with both chemical and crystal polymorph differences in the solid lipid matrix cited as controlling factors in drug release rates. This work uses model formulations composed of crystalline caffeine embedded in tristearin to study the impacts to drug release from the two primary polymorphic states of tristearin and dependencies on the conversion routes between them. Using contact angles and NMR diffusometry, this work finds that drug release from the meta-stable α-polymorph is rate limited by a diffusive mechanism relating to its porosity and tortuosity, but initial burst release occurs due to ease of initial wetting. Poor wettability resulting from surface blooming can be rate limiting for the β-polymorph, resulting in slower initial drug release relative to the α-polymorph. The route to achieve the β-polymorph strongly impacts the bulk release profile due to differences in crystallite size and packing efficiency. API loading enhances the effective porosity, leading to enhanced drug release at high loadings. These findings offer generalizable principles to guide formulators on the types of impacts to drug release rates that one may expect due to triglyceride polymorphism.

β-tricalcium phosphate/gelatin composite scaffolds incorporated with gentamycin-loaded chitosan microspheres for infected bone defect treatment.

The repair of infected bone defects remains a clinical challenge. Staphylococcus aureus is a common pathogenic micro-organism associated with such infections. Gentamycin (GM) is a broad spectrum antibiotic that can kill S. aureus in a dose-dependent manner. However, the systemic administration of antibiotics may lead to drug resistance and gut dysbiosis. In this work, we constructed β-tricalcium phosphate/gelatin composite scaffolds incorporated with gentamycin-loaded chitosan microspheres (CMs(GM)-β-TCP/gelatin composite scaffolds), which helped optimize the local GM release in the infected defect areas and enhance bone regeneration. The cumulative release curves showed that both microspheres and composite scaffolds reached a sustained slow-release phase after the initial rapid release, and the latter further stabilized the initial drug release rate. The release curve of CMs(GM)-β-TCP/gelatin composite scaffolds reached a plateau after 24 h, and the cumulative release reached 41.86% during this period. Moreover, the combination of β-TCP and gelatin mimicked bone composition and were able to provide the requisite mechanical strength (0.82 ± 0.05 MPa) during the first phase of bone generation. The inner structure of the scaffold was arranged in the shape of interconnected pores, and presented a porosity level of 16%. The apertures were uniform in size, which was beneficial for cell proliferation and material transportation. Macroscopic observation and histological analysis showed that CMs(GM)-β-TCP/gelatin composite scaffolds fused with bone tissues, and new tissues were formed in defect areas without any infection. This new composite scaffold may be a promising repair material for treating infected bone defects.

Fabrication and In Vitro Evaluation of Febuxostat Tablet for Obtaining Biphasic Drug Release Profile.

Aim and Objective The primary aim of the present investigation was to adopt the concept of quality by design (QbD) for developing Febuxostat matrix tablets containing a novel combination of polyethylene oxide (PEO), pre-gelatinized starch (PGS) and lactose for obtaining biphasic drug release. Experimental work Febuxostat-containing matrix tablets were prepared by direct compression using 32 full factorial designs. The tablets were prepared with varying amounts of PEO WSR 301 to PGS and lactose to obtain the desired release pattern. The chosen responses were cumulative % drug released at 1, 6 and 12 hours. The evaluation of tablets was done for pre and post-compressional parameters. Compared with the marketed tablet, the optimized formulations were selected based on in vitro drug release. Dose dumping was checked in the dissolution medium containing up to 40% alcohol. Result and discussion The results of the dissolution study indicated that the batch containing a 1:1 ratio of PEO WSR 301 and PGS (15 mg each) and 20 mg of Lactose showed fast initial drug release to imitate the pharmacological action followed by sustained drug release effect. The use of Lactose facilitated immediate drug release, while PEO WSR 301 and PGS exhibited the opposite effect on cumulative drug release. The results of the 32 Factorial design revealed that the concentration of Lactose is a critical parameter. Dose dumping was not observed in the alcoholic dissolution medium. Kinetic equations were fitted to the dissolution data after 1 hour of the dissolution study. Conclusion The type (soluble or swellable) and the concentration of excipients (low or high) dictate the tablets' drug release. The study's outcome revealed that the most critical material attribute is the amount of lactose. The novel combination of PEO, PGS and lactose can bypass existing patents and give more industrial applicability.