Development and In-Vitro characterization of risperidone loaded hydroxy propyl beta cyclodextrin nanosponge for enhancing bioavailability

Purpose: To develop and evaluate nanosponge (NS) based sustained release formulations of naproxen (NAP) and ibuprofen (IBU).Method: Six formulations of each candidate drug were prepared by emulsion solvent diffusion method, using varying ratios of polymers, i.e., ethyl cellulose and polyvinyl alcohol. The prepared formulations were evaluated for various parameters including production yield, particle size, polydispersity index, actual drug content and entrapment efficiency. Morphological, structural and thermo-analytical evaluations were performed using various techniques. In vitro release studies were performed on selected formulations.Results: Nanosponge (NS) formulations of naproxen and ibuprofen were successfully prepared by emulsion solvent diffusion method. The particle size of naproxen and ibuprofen nanosponge formulations ranged from 347.6 to 1358 nm and 248.7 to 327.6 nm, respectively. Formulations with equal proportion of ethyl cellulose and drug resulted in nanosponges with the desired particle size. Production yield, actual drug content and entrapment efficiency was dependent on the ratio of ethyl cellulose and polyvinyl alcohol. Formulations with equal proportion showed least PDI values (0.09 for NAP and 0.07 for IBU) and highest zeta potential (-27.2 mV for NAP and -28.2 mV for IBU). Morphological, structural and thermo-analytical analysis confirmed the encapsulation of drugs in nanosponge cavities, and exhibited spherical and porous morphology. Nanosponge formulations gave a sustained release pattern, based on Higuchi model. Drug release mechanism was Fickian followed Korsmeyer-Peppas model, due probably to the porosity of the nanosponge.Conclusion: Sustained release nanosponge formulations of naproxen and ibuprofen have successfully been prepared.Keywords: Nanosponge, Naproxen, Ibuprofen, Emulsion solvent diffusion method, Sustained release

Polymeric microspheres of gliclazide were prepared to provide sustained release delivery of gliclazide to aid in continuous therapy with high margin of safety. Gliclazide was microencapsulated with different polymers namely HPMC K100LV, Ethocel (20 cps) and HPMC K100M by emulsion solvent evaporation technique using acetone as internal phase and liquid paraffin as external phase. Seventeen formulations were prepared using different drug loading and polymeric ratio of which nine formulations were prepared by a 32 full factorial design. Each formulation was evaluated for flow properties, particle size, surface morphology, drug entrapment efficiency, drug release and compatibility. Yield (%) for every batch of microspheres was measured. Flow properties of the microspheres were examined by determining bulk density, tapped density, Carr’s compressibility index, Hausner ratio and angle of repose. Particle size distribution was examined by sieving and particle size analyzer. Surface morphology was determined by scanning electron microscopy (SEM). In-vitro drug release was studied in a paddle type dissolution apparatus (USP Type II Dissolution Apparatus) for a period of 8 hours at 37°C using phosphate buffer ( pH 7.4). FTIR and DSC studies established compatibility of the drug with the polymers. Microspheres prepared with Ethocel (20 cps) and HPMC K100M were free flowing than those prepared only with HPMC K100LV. Entrapment efficiencies were within 75.88-99.69%. Microspheres prepared with Ethocel (20 cps) and HPMC K100M showed more sustained release when compared to microspheres prepared with HPMC K100LV only. Increase in drug loading resulted in increased drug release for the microspheres. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranging from diffusion controlled to anomalous type. Ethocel and HPMC K100M in a ratio of 1:3 exhibited better sustained release properties than 1:1 and 3:1 ratios. The release rate of gliclazide from microspheres prepared with Ethocel (20 cps) and HPMC K100M was less than the release rate of gliclazide from microspheres prepared with HPMC K100LV, demonstrating Ethocel and HPMC K100M as suitable polymeric blend for preparing the controlled release formulation for gliclazide whereas, HPMC K100LV was found not suitable candidate when used alone as a polymer. DOI: http://dx.doi.org/10.3329/dujps.v13i2.21893 Dhaka Univ. J. Pharm. Sci. 13(2): 149-166, 2014 (December)

In the entire world, hepatocellular carcinoma (HCC) is the second leading cause of cancer death and the fifth prevalent kind of cancer. For hepatocellular carcinoma, herbal microsphere formulations may be more beneficial than conventional formulations due to their improved component solubility, increased bioavailability, and lower dosage, ability to maintain a therapeutic dose over time, improved stability, and protection against chemical and physical degradation. Combining curcumin with linalool formulations might have a synergistic impact.This preliminary research work is proposed for the formulation and characterization of a linalool and curcumin-co-loaded microparticulate system for hepatocellular carcinoma. The characterization of linalool and curcumin as pure drugs was done by UV spectroscopy and FTIR. The microspheres containing curcumin and linalool were characterized in terms of drug release, entrapment efficiency, zeta potential, particle size, and photomicroscopy and FTIR. Model-fitting curves, including the zero-order, first-order, Korsmeyer-Peppas, Higuchi, and Hixson-Crowell models, were used to study the mechanism of drug release. Out of all the formulations, Formulation F2 was accepted. Good drug release and trapping efficiency were found in Formulation F2. Drug release was found to be at its highest when linalool and chitosan concentrations rose, as was the scenario with release also.

Objective: The purpose of the present investigation was to develop and characterize a novel herbal formulation (polymeric microspheres) of Syzygium cumini seed extract.Methods: The extract-loaded microspheres using biological macromolecule ethyl cellulose (EC) was prepared by o/w emulsion solvent evaporation technique using polyvinyl alcohol (PVA) emulsifier. The effect of various process and formulation variables (stirring speed, evaporation time, drug/polymer ratio and organic/aqueous phase ratio) on the properties of microspheres was evaluated.Results: Micromeritic properties indicated good flow properties, and scanning electron microscopy (SEM) confirmed the spherical nature of the prepared microspheres. The particle size and entrapment efficiency were varied between 34.25 to 176.25 µm and 10.51 to 42% depending upon the variables. All the formulations showed minimal drug release in an acidic environment (pH 1.2) confirming the prevention of drug release in the stomach and enteric nature of the polymer. Sustained drug release has been observed in alkaline dissolution media (pH 7.4) after 12 h of drug release study except for formulation F7 which contains a lower concentration of polymer. The fourier transform infrared spectroscopy (FTIR) analysis indicated the compatibility of the extract with the polymer. The absence of extract-polymer interaction was indicated by the differential scanning calorimetry (DSC) thermogram. x-ray diffraction (XRD) analysis revealed the amorphous nature of the extract in the microspheres which in pure form exhibits a crystalline structure.Conclusion: The findings of this present study suggest that microsphere formulation was a promising carrier for novel delivery of herbal drugs.

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.

Objective: The purpose of this research work is to formulate and optimize mucoadhesive microspheres of nifedipine using Carbopol 934P as mucoadhesive and ethyl cellulose as a carrier polymer for controlling the release of nifedipine.
 Methods: The emulsion solvent evaporation technique was used for the preparation of microspheres and the 32 full factorial designs were employed for optimization of microspheres. The developed microspheres were characterized for percent yield, entrapment efficiency, particle size, in vitro release study, percent mucoadhesion, surface morphology, and stability study.
 Results: Evaluating outcomes of preliminary batches indicated that 100 ml volume of processing medium, 5 h stirring time and 2% concentration of emulsifying agent were suitable for spherical, free-flowing microspheres and high percentage drug entrapment efficiency. The optimized batch exhibited 84.35% drug entrapment efficiency, 61.78% mucoadhesion and drug release were also sustained for more than 12 h. Scanning electron microscopy study revealed that produced microspheres were spherical in shape.
 Conclusion: Experimental responses of the optimized batch have close proximity with the predicted value and stability study of the optimized formulation proved the formulation is stable for a long period of time; hence, it is an excellent alternative over the conventional delivery system.

Abstract: Background: Baclofen is used as skeletal muscle relaxant. Baclofen inhibit Polysynaptic and monosynaptic reflexes a hyperpolarisation. Baclofen drug absorbed rapidly and excreted in feces urine in unchanged form. Objectives: Aim of the current study was to formulate sustained release mucoadhesive microcapsules of Baclofen using different polymers like Chitosan, Carbopol934P, HPMC K4M. Materials and Methods: Ionotropic gelation method was used for preparation of microcapsules of baclofen. Dispersion of polymers and baclofen was dropwise added sodium tripolyphosphate solution to form microcapsule. The prepared microcapsules were evaluated for FTIR studies, micromeritic properties, drug entrapment efficiency, particle size and shape, SEM, swelling index, mucoadhesive strength, in vitro release studies. Results: Angle of repose of prepared microcapsules was in range 24.48 ± 1.39 to 38.08±1.67 showed good flowability. Prepared microcapsules showed bulk density in the range of 0.49±0.04 to1.22±0.06. All formulations showed Carr’s index and Hausner’s ratio in the range of 14.68 ±1.20 to 29.56 ± 1.97 and 1.16±0.012 to 1.25±0.016 respectively. Formulation F1 to F3 prepared with HPMC (K4M) showed drug release 77.78%, 74.94%, 77.99% and formulation F4 to F6 prepared with Carbopol 934P showed drug release 78.20%, 79.05%, 87.48% respectively in 12hr. Conclusion: Sustained release profile F6 formulation was obtained due to significant mucoadhesive efficiency of the Carbopol 934P. Hence the mucoadhesive microcapsules of Baclofen would be an effective strategy for the management of Muscle Pain. Keywords: Baclofen, Microcapsule, Carbopol 934P, HPMC K4M, Sustained Release.

Objective: This project aims to develop and evaluate solid lipid nanoparticles (SLNs) of an antiviral drug to improve bioavailability, reduce dosing frequency, and enhance patient compliance. SLNs offer a nanocarrier system that addresses the poor solubility, low oral bioavailability, and systemic side effects associated with conventional antiretroviral therapy. Methods: SLNs of dolutegravir were prepared using high shear homogenization followed by ultrasonication. Biocompatible lipids such as glyceryl monostearate were used as the lipid matrix, and Poloxamer 188 served as the stabilizer. To optimize the formulation, lipid content, surfactant type, concentration, and sonication parameters were systematically varied. The prepared formulations were evaluated for particle size, zeta potential, drug entrapment efficiency, and in-vitro drug release profile to determine the optimum conditions for SLN development. Results: The optimized solid lipid nanoparticle (SLN) formulation exhibited a particle size in the range of 257–412 nm with a negative zeta potential (ZP), indicating good physical stability and low aggregation tendency. A high drug entrapment efficiency (%EE) (>85%) confirmed effective incorporation of the drug within the lipid matrix. In vitro release studies demonstrated a biphasic release pattern, characterized by an initial burst release followed by sustained drug release over 24 hours. Differential Scanning Colorimetry (DSC) and Fourier Trasform Infrared Spectrocopy (FTIR) analyses revealed no significant drug–lipid interactions, confirming formulation compatibility. Transmission Electron Microscopy (TEM) analysis showed spherical nanoparticles with smooth surfaces and uniform morphology. Overall, the formulation displayed desirable physicochemical and release characteristics suitable for sustained drug delivery. Conclusion: The study demonstrates that solid lipid nanoparticles (SLNs) are a promising delivery system for antiretroviral drugs, offering sustained release, improved pharmacokinetic behavior, and reduced dosing frequency. However, further in vivo studies are required to confirm their therapeutic efficacy and biodistribution profile.

Objective: The main aim of the present investigation was to develop sustained release microbeads of ritonavir that has a shorter half-life (3-5 h) and requires twice a day administration. These formulations exhibit a sustained release of ritonavir that would expect to improve the therapy, better drug utilization, and patient compliance.
 Methods: Gellan-chitosan and calcium chloride reinforced beads of ritonavir were prepared by ionotropic gelation method employing different concentrations of gellan, chitosan, calcium chloride and drug. The prepared beads were evaluated for various physicochemical parameters such as particle size determination, drug entrapment efficiency, swelling studies, infrared spectroscopy study, differential scanning calorimetry, x-ray diffraction analysis, scanning electron microscopy, in vitro drug release study and in vivo bioavailability studies.
 Results: From the results, formulation GC-II exhibited higher drug entrapment efficiency (79.65±0.012), higher swelling index, sustained drug release over a period of 24 h, increased oral bioavailability (2.07 times higher than that of pure drug) and decreased elimination rate (2.15 times lesser for ritonavir microbeads) with prolonged elimination half-life (2.15 times more than pure drug) as compared to pure drug.
 Conclusion: Ritonavir microbeads have demonstrated as a better delivery system for the sustained release of the drug; which may in turn circumvent the drawbacks associated with the conventional therapy.

This study aimed to develop nitrofurantoin-loaded nanosponges to enhance solubility, prolong drug release, and improve antibacterial efficacy for the effective management of urinary tract infections (UTIs). Nanosponges were prepared using the emulsion solvent diffusion method with ethyl cellulose and Eudragit RS100 as polymers and eight formulations (F1–F8) were evaluated for particle size, zeta potential, drug content, entrapment efficiency, percentage yield, in-vitro release, antibacterial activity and stability. Among these, formulations F4 and F8 were identified as optimized batches, showing particle sizes of 442.0 nm and 345.9 nm, drug content of 94.20% and 96.87% and entrapment efficiencies of 94.84% and 96.9%, respectively. In-vitro release studies demonstrated sustained drug release of up to 94.7% over 8 hours, with release kinetics best described by the Korsmeyer–Peppas model, indicating diffusion-controlled release. Antibacterial testing against Escherichia coli revealed that F4 and F8 produced larger inhibition zones of 15 mm and 20 mm, respectively, compared with pure drug. Stability studies over 90 days further confirmed that the optimized formulations maintained their appearance and drug content without significant changes. Overall, nitrofurantoin nanosponges exhibited improved solubility, sustained release, high drug entrapment and enhanced antibacterial activity, demonstrating strong potential as advanced drug delivery systems for the effective treatment of UTIs.

Purpose: Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) which when administered via an oral route displays significant gastro-intestinal side effects and has low skin permeation profile. The objective of the present work is to utilise nanostructured lipid carriers (NLCs) as carrier system for transdermal delivery of ketoprofen. Methods: NLCs were prepared via hot homogenisation technique using bees wax, carnauba wax, glycerl monostearate (solid lipids), linseed oil (liquid lipid) and poloxamer188 (surfactant) and optimized using custom design via JMP. The responses evaluated were drug entrapment efficiency, particle size and drug release profile. The experimental design was evaluated for model fit with the assistance of ANOVA. The optimum formulations were characterized for particle size, zeta potential, SEM, DSC, FTIR and also drug content, entrapment efficiency, in- vitro drug release, ex-vivo drug release profile was studied. Results: The drug entrapment in the range of 34±0.03-95.06±0.01%. The drug release from the formulations over a 24 h study was found to be 80%±0.09 to 95%±0.06. The maximum desirability was found to be 0.91. The optimum formulation showed mean particle size of 425.8nm and a zeta potential of -45mV. SEM results revealed slightly agglomerated particles with uneven surfaces. The ex-vivo skin permeation of NLC optimized patch formulation exhibited a higher flux and permeability coefficient in comparison to the pure drug patch formulation and marketed gel (2.5%w/w) FTIR spectra assured the chemical and physical compatibility. Conclusion: Transdermal delivery of ketoprofen via NLCs would be a promising approach for improving the skin permeation.

Objective: Develop and evaluate mucoadhesive microspheres using Chitosan, Sodium alginate, and Sodium carboxymethyl cellulose (NaCMC) for sustained oral delivery of Metronidazole, aiming to improve bioavailability. Methods: Metronidazole-loaded microspheres were prepared via ionotropic gelation method with varying polymer ratios. Particle size, entrapment efficiency, swelling index, mucoadhesion (sheep mucosae), morphology (SEM), in-vitro wash-off test, drug release profile, and stability (6 months) were evaluated. Results: Chitosan content positively correlated with microsphere size. Entrapment efficiency ranged from 51.43% to 94.15%. Chitosan-based formulations, especially MTZ-7 (Chitosan:NaCMC, 3:1), displayed the highest mucoadhesion. SEM analysis revealed rough, spherical microspheres with a continuous polymeric coat. In-vitro wash-off test demonstrated prolonged residence time for Chitosan formulations. Sustained drug release was observed throughout the study, with MTZ-7 exhibiting the most desirable release profile. Stability studies showed no significant changes in drug release for selected formulations after 6 months. Conclusions: Chitosan-based microspheres, particularly MTZ-7, demonstrated superior mucoadhesive properties, sustained and controlled drug release, and desirable stability. These findings suggest the potential of Chitosan-based microspheres as a promising oral drug delivery system for Metronidazole, potentially addressing bioavailability concerns and improving therapeutic efficacy.

The aim of the present investigation was to prepare and evaluate gastroretentive floating microspheres of Verapamil hydrochloride that would retain the drug in stomach and continuously release the drug in controlled manner up to a predetermined time. Floating microspheres were prepared by emulsion solvent evaporation technique. In the present investigation three polymers were used in various concentrations; Methocel K4M, Methocel K15M and Methocel K100M. In vitro performance was evaluated by the usual pharmacopoeial and other tests such as particle size analysis, drug entrapment efficiency, flow properties, in vitro floatability studies, in vivo floatability studies in dog, in vitro drug release studies, stability studies etc. Results showed that the mixing ratio of components in the organic phase affected the size, size distribution, yield, drug content, floating time and drug release of microspheres. In most cases good in vitro floating behavior was observed and a broad variety of drug release pattern could be achieved by variation of the drug, polymer and solvent ratio.

Structure and Drug Release in a Crosslinked Poly(Ethylene Oxide) Hydrogel

Objective: The study was carried out with an objective to achieve a potential sustained release oral drug delivery system of an antihypertensive drug, Perindopril which is a ACE inhibitor having half life of 2 hours. Perindopril is water soluble drug, so we can control or delay the release rate of drug by using release retarding polymers. This may also decrease the toxic side effects by preventing the high initial concentration in the blood.Method: Microcapsules were prepared by solvent evaporation technique using Eudragit L100 and Ethyl cellulose as a retarding agent to control the release rate and magnesium stearate as an inert dispersing carrier to decrease the interfacial tension between lipophilic and hydrophilic phase. Results: Prepared microcapsules were evaluated for the particle size, percentage yield, drug entrapment efficiency, flow property and in vitro drug release for 12 h. Results indicated that the percentage yield, mean particle size, drug entrapment efficiency and the micrometric properties of the microcapsules was influenced by various drug: polymer ratio. The release rate of microcapsules could be controlled as desired by adjusting the combination ratio of dispersing agents to retarding agents.Conclusion:Perindopril microcapsules can be successfully designed to develop sustained drug delivery, that reduces the dosing frequency and their by one can increase the patient compliance.