FORMULATION AND EVALUATION OF PERINDOPRIL MICROENCAPSULES BY USING DIFFERENT POLYMER

This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 micrograms) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P > .05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P < .05), whereas metoprolol was indistinguishable from placebo (P > .05). The median cumulative salbutamol concentrations causing a 50% increase in specific airway conductance were 416 and 384 micrograms (days 1 and 7, respectively) for placebo, 594 and 444 micrograms for metoprolol, and 562 and 1419 micrograms for atenolol. The median cumulative salbutamol concentrations causing a 35% increase in tremor were 732 and 706 micrograms for placebo, 812 and 1213 micrograms for metoprolol, and 797 and 1323 micrograms for atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Quetiapine fumarate, an atypical antipsychotic drug, was subjected to comprehensive preformulation studies to evaluate its physicochemical properties and suitability for gastroretentive drug delivery. The drug was identified as a white to off-white, odorless crystalline powder with a bitter taste. Solubility studies revealed slight solubility in water and better solubility in organic solvents, indicating the need for formulation strategies to enhance its bioavailability. The melting point (182–184 °C), low loss on drying (1.56%), linear calibration curve obeying Beer–Lambert’s law, and characteristic FTIR peaks confirmed the identity, purity, and stability of Quetiapine fumarate. Gastroretentive microspheres loaded with Quetiapine fumarate were successfully prepared using the solvent evaporation technique by varying the ratios of HPMC and Eudragit RLPO. The prepared formulations (F1–F6) were evaluated for percentage yield, drug entrapment efficiency, buoyancy, floating lag time, particle size, zeta potential, and in-vitro drug release. Among all formulations, F3 emerged as the optimized formulation, exhibiting the highest percentage yield (86.65 ± 0.22%), drug entrapment efficiency (79.88 ± 0.15%), excellent buoyancy (85.6 ± 0.2%), and minimal floating lag time (60 ± 3 s). In-vitro drug release studies demonstrated a sustained release profile over 12 hours, following diffusion-controlled kinetics as indicated by Higuchi and Korsmeyer–Peppas models. Particle size and zeta potential analyses confirmed nanoscale size and good stability of the microspheres. Stability studies conducted as per ICH guidelines revealed no significant changes in physical appearance, drug content, or dissolution behavior. The optimized gastroretentive microspheres of Quetiapine fumarate showed promising characteristics for prolonged gastric retention and controlled drug release, suggesting their potential to enhance bioavailability, therapeutic efficacy, and patient compliance. Keywords: Gastroretentive microspheres; Quetiapine fumarate; Solvent evaporation method; Controlled drug release; Buoyancy; Stability studies.

In this study, we have evaluated the interactions of zein microspheres with different class of drugs (hydrophobic, hydrophilic, and amphiphilic) using in vitro and in silico analysis. Zein microspheres loaded with aceclofenac, metformin, and promethazine has been developed by solvent evaporation technique and analyzed for its compatibility. The physical characterization depicted the proper encapsulation of hydrophobic drug in the microspheres. The in vitro release study revealed the sustaining ability of the microspheres in the following order: hydrophobic > hydrophilic > amphiphilic. In silico analysis also confirmed the better binding affinity and greater interactions of hydrophobic drug with zein. The above results revealed that zein is more suitable for hydrophobic drugs in the development of sustained drug delivery systems using solvent evaporation technique. The study therefore envisages a scope for identifying the most suitable polymer for a sustained drug delivery system in accordance with the nature of the drug.

Liposomes have proven to be versatile carriers for the delivery of drugs. These carriers are biocompatible, since they are generally made from lipids commonly found in biologic systems and are biodegradable by the usual metabolic pathways. A sustained drug delivery system is useful when the efficacy of drugs is limited by the inability to maintain therapeutic concentrations. Furthermore, a depot delivery system can offer important advantages in the clinic, such as significantly reducing dose frequency and providing efficacy without toxicity. Because of their small size (<5μ.m), conventional liposomes (unilamellar and multilamellar) are limited in their ability to provide depot delivery of drugs when administered subcutaneously or intramuscularly. The small size of these liposomes results in relatively fast clearance from the injection site and a short duration of delivery, typically 1–4 days. Multivesicular liposomes (MVLs) are distinct from conventional liposomes in composition, structure, and size and are the only class of commercial liposomes that have demonstrated depot delivery of both small molecule and protein/peptide drugs. These MVLs are characterized by the presence of a continuous bilayer membrane, with numerous internal aqueous compartments that are contiguous and separated by bilayer septums. As a result of their larger size (median diameter typically 10–30μ.m), these MVLs are not rapidly cleared by tissue macrophages and can act as a drug depot providing slow release of drugs delivered through different routes of administration. Moreover, the biocompatibility and biodegradability of the MVL lipid matrix allows for the sustained delivery of drugs to sensitive areas. The unique architecture of MVLs provides high drug loading of water-soluble drugs, reasonable stability during storage, and control over the drug-release rate. Furthermore, the lipid composition of MVLs can be altered to deliver therapeutics over periods ranging from a few days to a month, in order to meet specific therapeutic needs. The capability of altering the rate of drug release from MVLs by varying the lipid composition provides a great deal of versatility for controlled delivery of a wide variety of therapeutics. This article reviews depot delivery with conventional liposomes, demonstrates through several examples the sustained depot delivery of small and macromolecular drugs using MVLs, and summarizes some novel delivery systems that combine liposomes with polymeric matrices and have the potential to expand the platform of liposomal depot delivery.

Introduction Glaucoma is a group of progressive optic neuropathies resulting in irreversible blindness. It is associated with an elevation of intraocular pressure (>21 mm Hg) and optic nerve damage. Reduction of the intraocular pressure (IOP) through the administration of ocular hypotensive eye drops is one of the most common therapeutic strategies. Patient adherence to conventional eye drops remains a major obstacle in preventing glaucoma progression. Additional problems emerge from inadequate patient education as well as local and systemic side effects associated with adminstering ocular hypotensive drugs. Areas covered Sustained-release drug delivery systems for glaucoma treatment are classified into extraocular systems including wearable ocular surface devices or multi-use (immediate-release) eye formulations (such as aqueous solutions, gels; ocular inserts, contact lenses, periocular rings, or punctual plugs) and intraocular drug delivery systems (such as intraocular implants, and microspheres for supraciliary drug delivery). Expert opinion Sustained release platforms for the delivery of ocular hypotensive drugs (small molecules and biologics) may improve patient adherence and prevent vision loss. Such innovations will only be widely adopted when efficacy and safety has been established through large-scale trials. Sustained release drug delivery can improve glaucoma treatment adherence and reverse/prevent vision deterioration. It is expected that these approaches will improve clinical management and prognosis of glaucoma.

The present study involves preparation and evaluation of gastric-mucoadhesive microparticles with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p (CP) and Ethylcellulose (EC). The microparticles were prepared by emulsion solvent evaporation method (O1/O2). Disc formulations were prepared by direct compression technique from microparticles. In the current study, gastric-mucoadhesive microparticles with different polymers ratios (CP:EC) were prepared and were characterized by encapsulation efficiency, particle size, flowability, mucoadhesive property and drug release studies. The best polymers ratio was 1:3 (F2) with Carbomer 934p (as mucoadhesive polymer) and ethylcellulose (as retardant polymer), respectively. The production yield microparticles F2 showed 98.80%, mean particle size 933.25 µm and loading efficiency %98.44. The results were found that microparticle discs prepared had slower release than microparticles (p > o.o5). The microparticles exhibited very good percentage of mucoadhesion and flowability properties. The release of drug was prolonged to 8 h (71.65-82.22%) when incorporated into mucoadhesive microparticles. The poor bioavailability of metformine is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract). The results of mucoadhesion study showed better retention of metformine microparticles (8 h) in duodenal and jejunum regions of intestine (F1, 1:2 ratio of CP:EC). Therefore, it may be concluded that drug loaded gastric-mucoadhesive microparticles are a suitable delivery system for metformin hydrochloride, and may be used for effective management of NIDDM (Non Insulin Dependent Diabetes Mellitus).

The objective of the present study was to develop floating microspheres of Captopril in order to achieve an extended retention in the upper GIT which may enhance the absorption and improve the bioavailability. In the present study, preparation of captopril floating microspheres, evaluation of Floating Drug Delivery System (FDDS) in vitro, forecast of the release, and optimization of stirring speed and polymers ratio to match target release profile was investigated. The microspheres were prepared by solvent evaporation method using different ratio of hydroxyl propyl methyl cellulose (HPMC K4M) with drug in the mixture dichloromethane and ethanol at ratio of (1:1), with tween80 as the surfactant. Differential Scanning Calorimeter (DSC) study shows that drug and other excipients are compatible with each other. The effects of polymers concentration on drug release profile were investigated. The floating microspheres were characterized by and results obtained are % yield, particle size analysis, drug entrapment efficiency, surface topography, buoyancy percentage, in-vitro drug release was studied for 12 hour and scanning electron microscopy. Accelerated stability study was also performed for three months indicated that optimized formulation was stable. The floating microspheres showed better result and it may be use full for prolong the drug release in stomach and improve the bioavailability. The outcome showed that the polymer ratio and stirring speed affected the size, incorporation efficiency and drug release of microspheres (&gt; 12 h), floating time (&gt; 12 hr) and the best results were obtained at the ratio of HPMC K4M: EC (1:6). The mean particle size of prepared floating microspheres increased but the drug release rate from the microspheres decreased as the polymer concentration increased. The developed floating microspheres of captopril may be used for prolonged drug release for at least 12 hrs, thereby improving the bioavailability and patient compliance. Key words: Floating microspheres (FDDS), captopril, hydroxyl propyl methyl cellulose, ethyl cellulose, in-vitro release studies, bioavailability.

The present study aimed to prepare hydrogel based on polyvinyl alcohol (PVA) and gelatin (Ge) and characterization of PVA/Ge hydrogel for their potential use as a sustained drug delivery system. Polyvinyl Alcohol (PVA) and-Gelatin (Ge) were cross-linked using glutaraldehyde (GA) as a crosslinking agent and hydrochloric acid (HCl) as a catalyst. Different feed polymer ratio and crosslinking agent concentration were used to prepare a series of PVA/Ge hydrogels. The obtained PVA/Ge hydrogels were investigated for dynamic and equilibrium swelling studies. The effect of polymers ratio, degree of crosslinking and pH of the medium on swelling of PVA/Ge hydrogels was investigated. Furthermore, the values of diffusion coefficient (D), volume fraction, polymer-solvent interaction parameter, molecular weight between crosslink and crosslink density were calculated. For swelling studies, 0.05M USP phosphate buffer solutions of different pH (1.2, 5.5, 6.5 and 7.5) were used. For the drug release study, ciprofloxacin HCl was loaded into selected samples as a model drug. The release of drug from these samples was performed for 12 hours in USP phosphate buffers of pH 1.2, 5.5 and 7.5. The release data from these samples were fitted into various kinetic models like zero order, first order, Higuchi and Peppas models to investigate the release mechanism. It was found that by varying the composition of PVA/Ge hydrogel and GA concentration, a significant difference was observed in drug release kinetics. FTIR spectroscopy and X-ray diffraction were used for the characterization of hydrogels. PVA/Ge hydrogel showed sustained release of the model drug at various pH values suggesting its potential use as a sustained drug delivery system.

The purpose of this study was to develop liposome-enriched Ketoprofen liposomal hydrogels and carry out in vitro release profile experiment. The aim was to achieve sustained topical drug delivery for extended time interval from liposomal gels. Phosphatidylcholine, Cholesterol and Ketoprofen were dissolved in chloroform/methanol (2:1, v/v) mixture and subsequently transferred to a flask attached to rotavapor. The liposomes were assessed for particle size and percent drug entrapment. F-7 and F-8 batches were found to be optimized batches having optimum sizes, drug entrapment efficiencies and cumulative drug releases. F-8 batch was further evaluated for stability. The results show that the prepared liposomes of Ketoprofen might turn out to be potential candidates for effective and safe sustained drug delivery thereby resulting in the reduction of dosing frequency.

Sustained release cellulose acetate (CA) and ethyl cellulose (EC) polymer blend nanofibers loaded with ketoprofen (KET) were successfully prepared by electrospinning. Successful fiber formation has been investigated by using two different binary solvent systems, i.e., acetic acid + distilled water (2:1 v/v) and acetone + N,N-DMAc + ethanol (2:1:1 v/v). Scanning electron microscopy (SEM) images showed that morphological features gradually change as the ratio of both polymers change. Nanofiber diameter also decreases as the CA content is increased in the polymer blend solution from 77.25 ±27 to 72.39 ±30 nm. Drug release profiles were evaluated by in-vitro drug release experiments. Drug release follows a pseudo-Fickian behavior of diffusion and shows a sustained release mechanism. Nanofibers containing more CA show greater controlled release capacity as compared to EC. X-ray diffraction (XRD) patterns of CA and EC polymer blend nanocomposites show that crystalline ketoprofen has changed into an amorphous state. Fourier transform Infrared (FTIR) analysis indicates hydrogen bonding occurs between the drug and the polymer, accounting for molecular integration of the two components. The thermal stability of the prepared polymer blend was also studied using thermo-gravimetric analysis (TGA). A polymer blend sustained release drug delivery system prepared by electrospinning make it possible to fabricate other novel drug releasing systems.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

Poly-e-caprolactone-loaded miglitol microspheres for the treatment of type-2 diabetes mellitus using the response surface methodology

Fluocinolone acetonide sustained drug delivery device to treat severe uveitis

The purpose of the study was to develop and evaluate risperidone loaded nanosponge having prolonged residence time and sustained drug release. Nanosponges were prepared by emulsification solvent evaporation technique using cyclodextrins polymers in varying ratios. The nanosponges were evaluated for its percentage yield, drug entrapment efficiency, particle size and shape and In vitro drug release studies. The FTIR studies revealed uniform caging of the drug into the beta cyclodextrin cavity. The cyclodextrin based nanosponge showed particle size, drug entrapment efficiency and yield in the ranges of 148 - 164μm, 68.0 - 85.0% and 67.52 - 87.25% respectively. In vitro drug release confirms that formulation F2 was the best formulation as it was discovered that the nanosponge formulation's % release was 98.17±0.31% for 60 mins. This confirms the developed nanosponges are promising and have better bioavailability.

Introduction: Novel drug delivery systems, which stabilize and enhance bioactivity, have significantly enhanced the delivery of herbal bioactives. This study aims to formulate and characterize ethyl cellulose microspheres loaded with hydroalcoholic Camellia sinensis (CS) extract to evaluate their antioxidant potential. Methods: Maceration, Soxhlet extraction, and decoction were used to optimize the extraction process based on the qualitative and quantitative phytochemical contents. Microspheres were formulated using solvent evaporation techniques with ethyl cellulose as the polymer, and their antioxidant activity was assessed. Prepared microspheres were characterized by FTIR, DSC, SEM, etc., followed by antioxidant assessment. Entrapment efficiency and release kinetics were studied based on the detection of quercetin-like compounds. Results: The macerated extract was chosen for formulation due to its high total phenolic content (376.44±0.012 mg GAE/g) and flavonoid content (249.42±0.46 mg QE/g). LC-MS analysis revealed the presence of numerous bioactive compounds, including epigallocatechin, epigallocatechin gallate, glutathione amide, etc. SEM analysis revealed porous and spherical microspheres. Formulation F5 exhibited the highest entrapment efficiency and demonstrated a sustained zeroorder release profile. In the DPPH scavenging assay, the microspheres (F1-F5) have shown significant antioxidant activities with IC50 values of 43.61±2.15; 45.58±3.72; 47.50±1.09; 46.87±3.31 and 45.35±1.24 μg/mL, respectively, compared to ascorbic acid 27.21±0.96 μg/mL. Similarly, a significant reducing power was observed with formulations (F1-F5) 85.58±4.59; 74.74±4.13; 65.47±3.96; 73.47±5.23 and 72.42±6.57 mg AAE/g, respectively, compared with CSE (92.74±7.54 mg AAE/g). method: Extraction was carried out using different extraction techniques such as maceration, Soxhlet and decoction. Pre-liminary phytochemical screening, total phenolic and flavonoids contents were assessed to select the best extraction procedure based on their contents. Microspheres was prepared using solvent evaporation techniques using ethyl cellulose as polymer. Formulated microspheres were evaluated for antioxidant potential by % DPPH radical scavenging and Reducing power assay. Microspheres were then characterized by FTIR, DSC, SEM etc. Entrapment efficiency and drug release study were also performed. Discussion: Microspheres formulated using macerated CS extract exhibited strong antioxidant properties, showed porous morphology with a zero-order release profile (F5), and confirmed a sustained and effective antioxidant delivery. Conclusion: Macerated Camellia sinensis extract-loaded microspheres offer a novel approach for delivering heat-sensitive compounds, providing sustained antioxidant benefits compared to traditional hot beverages, which can lose thermolabile compounds during preparation.