Preparation and evaluation of a novel gastric mucoadhesive sustained-release acyclovir microsphere

Objective: The objective of this study was to prepare a novel gastric mucoadhesive sustained-release acyclovir (AV)-resinate microsphere. Methods: First, AV absorption ratio was quantified in a rat gastrointestinal (GI) tract model. AV-resinate was prepared by bath method and used as cores to prepare microspheres by an emulsion solvent diffusion technique with carbopol 934 as coating material. GI transit test of the prepared microspheres was carried out in rats and beagle dogs, followed by the in vivo bioavailability evaluation of the microspheres in beagle dogs. Results: The AV absorption ratio in different segments of rat's GI track for 3 hours was as following: stomach 9.46 ± 0.62%, duodenum 20.22 ± 1.50%, jejunum 15.7 ± 1.33%, ileum 9.15 ± 1.01%, and colon 4.59 ± 0.48%. These results showed that AV was mainly absorbed in the stomach and upper intestine. The average diameter of the microspheres was 115.3 μm. The microspheres had a drug content of 33.3 ± 0.7% (w/w) and a sustained-release profile for 12 hours in vitro. The mucoadhesive test in rats and beagle dogs showed that most of the microspheres were retained in the stomach 6 hours after oral administration. The in vivo pharmacokinetics test revealed that the microsphere and reference (AV tablets) preparations have no significant difference for C_max. The t_max has increased from 2.33 hours (reference) to 5 hours (test). Meanwhile, the relative bioavailability of AV microspheres was 145%. Conclusion: A novel AV-resinate microsphere was prepared. The microspheres were proved to be gastric mucoadhesive and sustained-release with higher bioavailability.     

Preparation,characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting

Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder manifested by cognitive, memory deterioration and variety of neuropsychiatric symptoms. Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD. The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly(lactic-co-glycolic acid) (PLGA) for sustained release and efficient brain targeting.

Materials and methods: PLGA nanoparticles (NPs) were prepared by the solvent emulsification diffusion–evaporation technique and characterized for particle size, particle-size distribution, zeta potential, entrapment efficiency, drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques.

Results and discussion: The size of drug-loaded NPs (drug polymer ratio 1:1) was found to be 89.67?±?6.43?nm. The TEM and SEM images of the formulation suggested that particle size was within 20–100?nm and spherical in shape, smooth morphology and coating of Tween-80 on the NPs was clearly observed. The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release. The biodistribution studies of donepezil-loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution (p?Conclusion: The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD. But further, more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system.     

Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin

Purpose: To examine effects of polymer types on the mucoadhesive properties of polymer-coated nanostructured lipid carriers (NLCs).

Experiment: Curcumin-loaded NLCs were prepared using a warm microemulsion technique followed by coating particle surface with mucoadhesive polymers: polyethylene glycol400 (PEG400), polyvinyl alcohol (PVA), and chitosan (CS). The physicochemical properties and entrapment efficacy were examined. In vitro mucoadhesive studies were assessed by wash-off test. In addition, the stability of mucoadhesive NLCs in gastrointestinal fluids and the pattern of drug release were also investigated.

Findings: The obtained nanoparticles showed spherical shape with size ranging between 200?nm and 500?nm and zeta potential between ?37 and ?9?mV depending on the type of polymer coating. Up to 80% drug entrapment efficacy was observed. In vitro mucoadhesive studies revealed that PEG-NLCs and PVA-NLCs were adhered strongly to freshly porcine intestinal mucosa, more than 2-fold mucoadhesive compared to CS-NLCs and uncoated-NLCs. The particle size of all polymer-coated NLCs could be maintained in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggesting good physical stability in physiological fluid. In contrast, uncoated-NLCs showed particle aggregation in SGF. In vitro dissolution studies revealed a fast release characteristic.     

Phospholipid–polymer hybrid nanoparticle-mediated transfollicular delivery of quercetin: prospective implement for the treatment of androgenic alopecia

Abstract

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia.

Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies.

Key findings: Hybrid NPs had mean vesicles size 339?±?1.6, zeta potential –32.6?±?0.51, and entrapment efficiency 78?±?5.5. Cumulative drug release after 12?h was found to be 47.27?±?0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis.

Conclusion: This study concludes that phospholipid–polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.     

Formulation development and evaluation of nifedipine as pylorospasm inhibitor

Introduction: In this study, different nifedipine-loaded formulations were prepared to treat pylorospasm, a sphincter muscle disorder characterized by delayed gastric emptying process. The efficacy of formulation was evaluated in patients by subjective assessment, gamma scintigraphic approaches, and confocal microscopy.

Methods: Nifedipine-loaded different formulations such as sucrose bead, pellets, and microparticles (slugging method, ionotropic gelation, and chemical denaturation) were designed. The studies were performed on 50 subjects, of which 30 subjects were treated with optimized nifedipine loaded microcapsules while 20 subjects were given capsule becosule-Z as a control. The efficacy of formulation was assessed by comparing symptoms like dyspepsia, abdominal pain, abdominal fullness, poor appetite, nausea, vomiting, and irregular motion. The effectiveness of formulation was also assessed by gamma scintigraphic studies by determining the rate of emptying of a radioactivity labeled standard meal from patients’ stomach into the duodenum. Confocal microscopy was used to assess targeting potential of developed formulation.

Results: Drug-loaded alginate-chitosan microcapsules were found to be satisfactory, in terms of controlled drug release, surface morphology, and bioadhesive properties and thus selected for in vivo studies. Clinical studies revealed the efficacy of formulation in abolishing various GI symptoms at high altitude. Associated symptoms such as dyspepsia, abdominal pain, poor appetite, nausea, vomiting, and irregular motion were recovered by 75, 62, 76.5, 86.7, 85.7, and 37.5%, respectively in nifedipine-treated patients. In comparison, 73.7, 40, 33.3, 40, 20, and 0% recoveries were observed in patients given control treatment only. Gamma Scintigraphic studies in lab also revealed 2.425?±?0.245 (p?Conclusions: Results strongly suggest that nifedipine loaded mucoadhesive formulation has a targeting potential which accelerates gastric emptying process in gastroparesis patients, and thus the formulation might prove useful as a potent prokinetic agent.     

Development and in vitro evaluation of floating rosiglitazone maleate microspheres

Background: Various approaches have been used to retain the dosage form in stomach as a way of increasing the gastric residence time, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extensible, or swellable systems; and superporous hydrogel systems. Aim?: The objective of this study was to prepare and evaluate floating microspheres of rosiglitazone maleate for the prolongation of gastric residence time. Method: The microspheres were prepared by solvent diffusion–evaporation method using ethyl cellulose and hydroxypropylmethylcellulose. A full factorial design was applied to optimize the formulation. Results: Preliminary studies revealed that the polymer:drug ratio, concentration of polymer, and stirring speed significantly affected the characteristics of microspheres. The optimum batch exhibited a prolonged drug release, remained buoyant for >12 hours, high entrapment efficiency, and particle size in the order of 350 μm. Conclusion: The results of 32 full factorial design revealed that the concentration of ethylcellulose 7 cps (X₁) and stirring speed (X₂) significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Design,characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Context: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Objective: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson’s drug ropinirole (RH) to the brain using polymeric nanoparticles.

Materials and methods: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration.

Results and discussion: The RH-CSNPs showed sustained release profiles for up to 18?h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210?±?0.52), followed by kidneys (6.862?±?0.62), intestine (4.862?±?0.45), and lungs (4.640?±?0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251?±?0.09 and 0.386?±?0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5?h are indicative of direct nose to brain transport, bypassing the blood–brain barrier (BBB).

Conclusion: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.     

Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers

Abstract

Objective: The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug.

Methods: Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI.

Results: In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37?±?1.02% within 45?min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be “<28% and <60%”, respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads.

Conclusions: DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.     

Development,optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis

Objective: Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis.

Significance: Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis.

Methods: The film was developed by using solvent casting technique and “Design of Experiments” approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior.

Results: Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04?±?2.4, swelling index 138.10?±?1.25, and folding endurance 270?±?3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7?days.

Conclusions: The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.     

Pharmacodynamic and pharmacokinetic investigation of cyclodextrin-mediated asenapine maleate in situ nasal gel for improved bioavailability

Asenapine maleate (AM) is used in the treatment of schizophrenia. Its oral and sublingual bioavailability is <2% and 35%, respectively, due to first pass metabolism and poor solubility. To avoid first pass metabolism and to enhance solubility at all nasal pH conditions, thermo-responsive in situ nasal gel containing asenapine maleate-hydroxyl propyl β cyclodextrin inclusion complex (AM-HPβCD) was prepared in the present study. Inclusion complex (1:1 molar ratio) was characterized using UV spectroscopy, FITR and XRD techniques. Selected formulation (F8b) contained a thermo-sensitive polymer poloxamer 407 which formed gel at 23%w/v concentration and a mucoadhesive polymer PVP K 30 (0.3%w/v) in temperature range of 29–34?°c. It was analyzed for pH, clarity, gelation temperature, mucoadhesive strength, gel strength and rheological parameters using Anton paar compact rheometer. This formulation was subjected to in vitro drug diffusion study using the Franz diffusion cell. Maximum % drug diffusion was obtained at the end of 120?min (99.1?±?0.44%w/v). Dissolution in simulated nasal fluid was 92.33?±?0.15%w/v at the end of 120?min. Locomotor activity was improved with nasal gel containing AM-HPβCD as compared to AM and AM-HPβCD oral solution in rats. C_max for nasal gel was found to be more (9?ng/ml) as compared to AM-HPβCD (5.5?ng/mL) and oral standard solution (2?ng/ml). T_max was found to be 1.5?h. AUC and thus bioavailability in rats by nasal route was increased by 2.5 fold.     

Solubility enhancement of miconazole nitrate: binary and ternary mixture approach

Context: Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations.

Objective: Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach.

Materials and methods: Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release.

Results: An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2?h from the mixtures of MN and polymers.

Discussion: Results revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD.

Conclusion: Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4?μg/ml to 57?640.0?μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.     

Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation

Abstract

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO₃) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO₃ were found to float immediately within 1?min and duration more than 9?h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67?h. Furthermore, the AUC_0?t of the floating mini-tablets (6849.83?±?753.80?h ng·mL^?1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16?±?924.60?h ng·mL^?1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.     

Cuboidal lipid polymer nanoparticles of rosuvastatin for oral delivery

The present work aimed to develop and characterize sustained release cuboidal lipid polymeric nanoparticles (LPN) of rosuvastatin calcium (ROS) by solvent emulsification-evaporation process. A three factor, two level (2³) full-factorial design was applied to study the effect of independent variables, i.e. amount of lipid, surfactant and polymer on dependent variables, i.e. percent entrapment efficiency and particle size. Optimized formulations were further studied for zeta potential, TEM, in vitro drug release and ex vivo intestinal permeability. Cuboidal nanoparticles exhibited average particle size 61.37?±?3.95?nm, entrapment efficiency 86.77?±?1.27% and zeta potential ?6.72?±?3.25?mV. Nanoparticles were lyophilized to improve physical stability and obtain free-flowing powder. Effect of type and concentration of cryoprotectant required to lyophilize nanoparticles was optimized using freeze-thaw cycles. Mannitol as cryoprotectant in concentration of 5-8% w/v was found to be optimal providing zeta potential ?20.4?±?4.63?mV. Lyophilized nanoparticles were characterized using FTIR, DSC, XRD and SEM. Absence of C=C and C–F aromatic stretch at 1548 and 1197?cm^?1, respectively, in LPN indicated coating of drug by lipid and polymer. In vitro diffusion of ROS using dialysis bag showed pH-independent sustained release of ROS from LPN in comparison to drug suspension. Intestinal permeability by non-everted gut sac model showed prolonged release of ROS from LPN owing to adhesion of polymer to mucus layer. In vivo absorption of ROS from LPN resulted in 3.95-fold increase in AUC_0–last and 7.87-fold increase in mean residence time compared to drug suspension. Furthermore modified tyloxapol-induced rat model demonstrated the potential of ROS-loaded LPN in reducing elevated lipid profile.     

Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV

Objective: To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF).

Significance: It may provide pre-exposure prophylaxis for women against HIV.

Methods: TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr’s index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies.

Results: Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague–Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40?±?2?°C and 75?±?5% RH for six months.

Conclusions: C1 was selected as the best formulation due to better swelling index (65.93% at 24?h), prolonged release of 100.62% cumulative drug release (CDR) at 24?h, superior mucoadhesion force (35.93?×?10² dynes/cm²) and retention time (16?h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.     

Formulation and evaluation of floating tablet of H2-receptor antagonist

Context: Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT.

Objectives: Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem.

Methods: Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3² factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32” flat-faced beveled edges punches followed by sublimation.

Results: FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60?K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12?h was found to be 420?mg of POLYOX and 40?mg of l-menthol. Stability studies indicated the formulation as stable.

Conclusion: Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12?h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.     

Development of electrosprayed artesunate-loaded core–shell nanoparticles

Objective: Artesunate (ART) is proven to have potential anti-proliferative activities, but its instability and poor aqueous solubility limit its application as an anti-cancer drug. The present study was undertaken to develop coaxial electrospraying as a novel technique for fabricating nanoscale drug delivery systems of ART as the core–shell nanostructures.

Methods: The core–shell nanoparticles (NPs) were fabricated with coaxial electrospraying and the formation mechanisms of NPs were examined. The physical solid state and drug–polymer interactions of NPs were characterized by X-ray powder diffraction (XRPD) and Fourier transform infrared (FTIR) spectroscopy. The effects of materials and electrospraying process on the particle size and surface morphology of NPs were investigated by scanning electron microscopy (SEM). The drug release from NPs was determined in vitro by a dialysis method.

Results: The ART/poly(lactic-co-glycolic) acid (PLGA) chitosan (CS) NPs exhibited the mean particle size of 303?±?93?nm and relatively high entrapment efficiency (80.5%). The release pattern showed an initial rapid release within two hours followed by very slow extended release. The release pattern approached the Korsmeyer–Peppas model.

Conclusions: The present results suggest that the core–shell NPs containing PLGA and CS have a potential as carriers in the anticancer drug therapy of ART.     

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads

Aim: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-β-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile.

Methods: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1?N HCl (pH 1.2) and phosphate buffer (pH 5.8).

Results: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730?±?0.05 to 0.890?±?0.03?mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12?h. The drug release from beads followed Fickian diffusion with swelling.

Conclusion: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.     

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets.

Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole.

Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X₁), sodium carboxy methylcellulose (X₂) and NaHCO₃ (X₃). The dependent variables were floating lag time (Y_FLT), cumulative percentage of metronidazole released at 6th h (Y₆) and cumulative percentage of metronidazole released at 12th h (Y₁₂). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed.

Results: Y_FLT range was found to be from 1.02 to 12.07?min. The ranges of other responses, Y₆ and Y₁₂ were 25.72?±?2.85 to 77.14?±?3.42 % and 65.47?±?1.25 to 99.65?±?2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage.

Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO₃ can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.     

Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice

Objective: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients.

Significance: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex^®), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique.

Methods: The formulation and procedure variables were optimized using Design Expert software, and effect of each variable on particle size, particle size distribution, drug entrapment efficiency, and drug release of the NPs were evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction pattern, and morphological characteristics of the optimized NPs were evaluated. Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing nude mice.

Results: The optimum condition for production of NPs included voltage of 20?kV, 12?cm distance between electrodes, feeding rate of 1?mL/hr, polymer to drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test confirmed no cytotoxic effect caused by blank NPs, while cell viability of the DTX loaded NPs was significantly lower than the free DTX (p?p?Conclusion: The Ecoflex^® NPs could potentially provide a suitable alternative for currently available formulations of DTX.