Chitosan nanoparticles for prolonged delivery of timolol maleate

Timolol maleate-loaded chitosan (CS) nanoparticles were prepared by desolvation method. Experimental variables such as molecular weight of CS and amount of crosslinking agent were varied to study their effect on drug entrapment efficiency, size and release rates of nanoparticles. Chemical stability of timolol maleate (TM) and crosslinking of CS were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetric studies were performed on drug-loaded nanoparticles to investigate crystalline nature of the drug after entrapment. Results indicated amorphous dispersion of drug in the polymer matrix. Scanning electron microscopy revealed irregularly shaped particles. Mean particle size of nanoparticles ranged between 118 and 203 nm, while zeta potential ranged between +17 and +22 mV. Entrapment efficiency of nanoparticles ranged between 47.6 and 63.0%. In-vitro release studies were performed in phosphate buffer saline of pH 7.4. A slow release of TM up to 24 h was observed. A 3² full factorial design was employed and second-order regression models were used to study the response (% drug release at 4 h). Release data as analyzed by an empirical relationship suggested that drug release deviated from the Fickian trend.     

Preparation and Optimization of Dry PLGA Nanoparticles by Spray Drying Technique

The aim of this article was to evaluate the potential of poly lactide-coglycolide (PLGA) nanoparticles (NPs) as carriers for controlling release of doxorubicin (DOX) via a spray drying technique. The challenge was to entrap a hydrophilic molecule into a lipophilic core molecule of PLGA. To achieve this objective, we modified conventional approach of drug loading to spray drying technique. The eight formulations of nanoparticles were prepared by modified double emulsion and solvent evaporation technique followed by spray drying using 2³ factorial designs. PLGA (A) and PVA (B) and stirring speed (C) were used as independent variables where particle size (Y₁), entrapment efficiency (Y₂) and percentage of drug release at the 32 hour (Y₃) were taken as dependant variables. The results showed that the method is easy and efficient for the entrapment of the drug as well as the formation of spherical nanoparticles. This modification improved DOX entrapment efficiency relative to controls real loadings up to 40%. The in vitro release studies indicated the DOX loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of DOX-PLGA nanoparticles.     

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Abstract

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0?±?2.4?nm to 257.2?±?18.6?nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10?mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p?<?0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.     

Facile development,characterization, and optimization of new metformin-loaded nanocarrier system for efficient colon cancer adjunct therapy

Purpose: Metformin hydrochloride (MF) repurposing as adjuvant anticancer therapy for colorectal cancer (CRC) proved effective. Several studies attempted to develop MF-loaded nanoparticles (NPs), however the entrapment efficiency (EE%) was poor. Thus, the present study aimed at the facile development of a new series of chitosan (CS)-based semi-interpenetrating network (semi-IPN) NPs incorporating Pluronic^® nanomicelles as nanocarriers for enhanced entrapment and sustained release of MF for efficient treatment of CRC.

Methods: The NPs were prepared by ionic gelation and subsequently characterized using FTIR, DSC, TEM, and DLS. A full factorial design was also adopted to study the effect of various formulation variables on EE%, particle size, and zeta-potential of NPs.

Results: NPs had a spherical shape and a mean particle size ranging between 135 and 220?nm. FTIR and DSC studies results were indicative of successful ionic gelation with the drug being dispersed in its amorphous form within CS-Pluronic^® matrix. Maximum EE% reaching 57.00?±?12.90% was achieved using Pluronic^®-123 based NPs. NPs exhibited a sustained release profile over 48?h. The MF-loaded NPs sensitized RKO CRC cells relative to drug alone.

Conclusion: The reported results highlighted the novel utility of the developed NPs in the arena of colon cancer treatment.     

Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel

Context: Polymeric carrier systems of paclitaxel (PCT) offer advantages over only available formulation Taxol® in terms of enhancing therapeutic efficacy and eliminating adverse effects. Objective: The objective of the present study was to prepare poly (lactic-co-glycolic acid) nanoparticles containing PCT using emulsion solvent evaporation technique. Methods: Critical factors involved in the processing method were identified and optimized by scientific, efficient rotatable central composite design aiming at low mean particle size and high entrapment efficiency. Twenty different experiments were designed and each formulation was evaluated for mean particle size and entrapment efficiency. The optimized formulation was evaluated for in vitro drug release, and absorption characteristics were studied using in situ rat intestinal permeability study. Results: Amount of polymer and duration of ultrasonication were found to have significant effect on mean particle size and entrapment efficiency. First-order interactions of amount of miglyol with amount of polymer were significant in case of mean particle size, whereas second-order interactions of polymer were significant in mean particle size and entrapment efficiency. The developed quadratic model showed high correlation (R² > 0.85) between predicted response and studied factors. The optimized formulation had low mean particle size (231.68 nm) and high entrapment efficiency (95.18%) with 4.88% drug content. The optimized formulation showed controlled release of PCT for more than 72 hours. In situ absorption study showed faster and enhanced extent of absorption of PCT from nanoparticles compared to pure drug. Conclusion: The poly (lactic-co-glycolic acid) nanoparticles containing PCT may be of clinical importance in enhancing its oral bioavailability.     

Formulation and in vitro evaluation of prolonged release floating microspheres of atenolol using multicompartment dissolution apparatus

The aim of the present work was to prepare floating microspheres of atenolol as prolonged release multiparticulate system and evaluate it using novel multi-compartment dissolution apparatus. Atenolol loaded floating microspheres were prepared by emulsion solvent evaporation method using 3² full factorial design. Formulations F1 to F9 were prepared using two independent variables (polymer ratio and % polyvinyl alcohol) and evaluated for dependent variables (particle size, percentage drug entrapment efficiency and percentage buoyancy). The formulation(F8) with particle size of 329?±?2.69 µm, percentage entrapment efficiency of 61.33% and percentage buoyancy of 96.33% for 12?h was the of optimized formulation (F8). The results of factorial design revealed that the independent variables significantly affected the particle size, percentage drug entrapment efficiency and percentage buoyancy of the microspheres. In vitro drug release study revealed zero order release from F8 (98.33% in 12?h). SEM revealed the hollow cavity and smooth surface of the hollow microspheres.     

Topical phenytoin nanostructured lipid carriers: design and development

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2³ factorial design. NLC formulations were characterized regarding their particle size (PS), zeta potential (ZP), entrapment efficiency percent (%EE), surface morphology, physicochemical stability, and in vitro release studies. The optimized NLC (F7) was further incorporated in 1%w/v carbopol gel and then characterized for appearance, pH, viscosity, stability, and in vitro drug release. The prepared NLCs were spherical in shape and possessed an average PS of 121.4–258.2?nm, ZP of (?15.4)–(–32.2)?mV, and 55.24–88.80 %EE. Solid-state characterization revealed that the drug is dispersed in an amorphous state with hydrogen bond interaction between the drug and the NLC components. NLC formulations were found to be stable at 25?°C for six months. The stored F7-hydrogel showed insignificant changes in viscosity and drug content (p>.05) up to six?months at 25?°C that pave a way for industrial fabrication of efficient PHT products. In vitro release studies showed a sustained release from NLC up to 48?h at pH 7.4 following non-Fickian Higuchi kinetics model. These promising findings encourage the potential use of phenytoin loaded lipid nanoparticles for future topical application.     

Development of Nitrendipine Controlled Release Formulations Based on SLN and NLC for Topical Delivery: In Vitro and Ex Vivo Characterization

The aim of the investigation is to develop solid lipid nanoparticles (SLN) and nano-structured lipid carrier (NLC) as carriers for topical delivery of nitrendipine (NDP). NDP-loaded SLN and NLC were prepared by hot homogenization technique followed by sonication, and they were characterized for particle size, zeta potential, entrapment efficiency, stability, and in vitro release profiles. Also the percutaneous permeation of NDPSLN A, NDPSLN B, and NDPNLC were investigated in abdominal rat skin using modified Franz diffusion cells. The steady state flux, permeation coefficient, and lag time of NDP were estimated over 24 h and compared with that of control (NDP solution). The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zeta sizer, which shows that the NDPSLN A, NDPSLN B, and NDPNLC were in the range of 124–300 nm during 90 days of storage at room temperature. For all the tested formulations (NDPSLN A, NDPSLN B, and NDPNLC), the entrapment efficiency was higher than 75% after 90 days of storage. The cumulative percentage of drug release at 24 h was found to be 26.21, 30.81, and 37.52 for NDPSLN A, NDPSLN B, and NDPNLC, respectively. The results obtained from in vitro release profiles also indicated the use of these lipid nanoparticles as modified release formulations for lipophilic drug over a period of 24 h. The data obtained from in vitro release from NDPSLN A, NDPSLN B, and NDPNLC were fitted to various kinetic models. High correlation was obtained in Higuchi and Weibull model. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations. The permeation profiles were obtained for all formulations: NDPSLN A, NDPSLN B, and NDPNLC. Of all the three formulations, NDPNLC provided the greatest enhancement for NDP flux (21.485 ± 2.82 μg/h/cm²), which was fourfold over control (4.881 ± 0.96 μg/h/cm²). The flux obtained with NDPSLN B (16.983 ± 2.91 μg/h/cm²) and NDPNLC (21.485 ± 2.82 μg/h/cm²) meets the required flux (16.85 μg/h/cm²).     

Study of Formulation Variables on Properties of Drug-Gellan Beads by Factorial Design

ABSTRACT

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3³ factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85–1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48–98.28% w/w and 72.52–92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12–35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3–4 h in pH 7.4 phosphate buffer.     

Development and optimization of locust bean gum and sodium alginate interpenetrating polymeric network of capecitabine

Objective: The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg).

Significance: The IPN microbeads were optimized by Box–Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle.

Methods: Ionotropic gelation method utilizing metal ion calcium (Ca²⁺) as a cross-linker was used to prepare IPN microbeads. The optimization study was done by response surface methodology based Box–Behnken Design. The effect of the factors on the responses of optimized batch was exhibited through response surface and contour plots. The optimized batch was analyzed for particle size, % drug entrapment, pharmacokinetic study, in vitro drug release study and further characterized by FTIR, XRD, and SEM. To study the water uptake capacity and hydrodynamic activity of the polymers, swelling studies and viscosity measurement were performed, respectively.

Results: The particle size and % drug entrapment of the optimized batch was 494.37?±?1.4?µm and 81.39?±?2.9%, respectively, closer to the value predicted by Minitab 17 software. The in vitro drug release study showed sustained release of 92% for 12?h and followed anomalous drug release pattern. The derived pharmacokinetic parameters of optimized batch showed improved results than pure CAP.

Conclusion: Thus, the formed IPN microbeads of CAP proved to be an effective extended drug delivery vehicle for the water soluble antineoplastic drug.     

Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: in vitro and in vivo characteristics

The purpose of this research was to investigate novel particulate carrier systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) for transdermal delivery of nitrendipine (NDP). For this investigation, four different gel-forming agents were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles made from trimyristin (TM) were prepared by hot homogenization technique followed by sonication and then incorporated into the freshly prepared hydrogels. The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zetasizer, which shows that for all the tested formulations, more than 50% of the particles were below 250 nm after 90 days of storage at room temperature. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed fairly spherical shape of the formulations. The antihypertensive activity of the gels in comparison with that of oral NDP was studied using desoxy corticosterone acetate (DOCA)-induced hypertensive rats. It was observed that both carbopol SLN (A1) and carbopol NLC (B1) gels significantly controlled hypertension from the first hour (p < .05). The developed gels increased the efficacy of NDP for the therapy of hypertension. Both the SLN and NLC dispersions and the gels enriched with SLN and NLC possessed a sustained drug release over a period of 24 h, but the sustained effect was more pronounced with the SLN and the NLC gel formulations. Further, they were evaluated for zeta potential, entrapment efficiency, in vitro release, ex vivo permeation, and skin irritation studies.     

Ciprofloxacin Liposomes as Vesicular Reservoirs for Ocular Delivery: Formulation,Optimization, and In Vitro Characterization

Management of extraocular diseases is mainly limited by the inability to provide long-term drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular system, for instance with liposomes. Development and optimization of reverse phase evaporation ciprofloxacin (CPF) HCl liposomes for ocular drug delivery was carried out using a 2⁵ full factorial design based on five independent variables. The effects of the studied parameters on drug entrapment efficiency (EE), particle size, and percentage of drug released after 1 and 10 h were investigated. The results obtained pointed out that the molar concentration of cholesterol was the predominant factor that increased the EE% of the drug and the particle size responses. The percentage of drug released after 1 h was significantly controlled by the initial CPF concentration while that after 10 h was controlled by molar cholesterol concentration. The designed liposomes had average particle sizes that ranged from 2.5 to 7.23 μm. In addition, liposomes revealed a fast release during the first hour followed by a more gradual drug release during the 24-h period according to Higuchi diffusion model.     

RES‐loaded pegylated CS NPs: for efficient ocular delivery

The objective of this study is to develop resveratrol (RES) loaded polyethylene glycols (PEGs) modified chitosan (CS) nanoparticles (NPs) by ionic gelation method for the treatment of glaucoma. While increasing the concentration of PEG, the particle size and polydispersity index of the formulations increased. Entrapment efficiency and RES loading (RL) of NPs decreased while increasing PEG concentration. The in vitro release of NPs showed an initial burst release of RES (45%) followed by controlled release. Osmolality of formulations revealed that the prepared NPs were iso‐osmolar with the tear. Ocular tolerance of the NPs was evaluated using hen''s egg test on the chorioallantoic membrane and it showed that the NPs were non‐irritant. RES‐loaded PEG‐modified CS NPs shows an improved corneal permeation compared with RES dispersion. Fluorescein isothiocyanate loaded CS NPs accumulated on the surface of the cornea but the PEG‐modified CS NPs crossed the cornea and reached retinal choroid. RES‐loaded PEG‐modified CS NPs reduced the intra‐ocular pressure (IOP) by 4.3 ± 0.5 mmHg up to 8 h in normotensive rabbits. These results indicate that the developed NPs have efficient delivery of RES to the ocular tissues and reduce the IOP for the treatment of glaucoma.Inspec keywords: conducting polymers, nanoparticles, nanomedicine, drug delivery systems, particle size, nanofabrication, organic compounds, biomembranes, cellular biophysics, eye, vision defects, biological tissuesOther keywords: RES‐loaded pegylated CS NP, efficient ocular delivery, resveratrol loaded polyethylene glycol modified chitosan nanoparticles, ionic gelation method, glaucoma treatment, particle size, polydispersity index, entrapment efficiency, RES loading, PEG concentration, in vitro release, osmolality formulations, ocular tolerance, hen egg testing, chorioallantoic membrane, improved corneal permeation, RES dispersion, fluorescein isothiocyanate loaded CS NP, cornea surface, reached retinal choroid, intraocular pressure, normotensive rabbits, RES delivery, ocular tissues     

Development of SLN and NLC Enriched Hydrogels for Transdermal Delivery of Nitrendipine: In Vitro and In Vivo Characteristics

The purpose of this research was to investigate novel particulate carrier systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) for transdermal delivery of nitrendipine (NDP). For this investigation, four different gel-forming agents were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles made from trimyristin (TM) were prepared by hot homogenization technique followed by sonication and then incorporated into the freshly prepared hydrogels. The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zetasizer, which shows that for all the tested formulations, more than 50% of the particles were below 250 nm after 90 days of storage at room temperature. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed fairly spherical shape of the formulations. The antihypertensive activity of the gels in comparison with that of oral NDP was studied using desoxy corticosterone acetate (DOCA)-induced hypertensive rats. It was observed that both carbopol SLN (A1) and carbopol NLC (B1) gels significantly controlled hypertension from the first hour (p < .05). The developed gels increased the efficacy of NDP for the therapy of hypertension. Both the SLN and NLC dispersions and the gels enriched with SLN and NLC possessed a sustained drug release over a period of 24 h, but the sustained effect was more pronounced with the SLN and the NLC gel formulations. Further, they were evaluated for zeta potential, entrapment efficiency, in vitro release, ex vivo permeation, and skin irritation studies.     

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.     

Sustained release microspheres of diclofenac sodium using PEGylated rosin derivatives

The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier (Nande et al., 2006) were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d(90)) ranged between 11-24 microm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size--small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n approximately 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.     

Sustained Release Microspheres of Diclofenac Sodium Using PEGylated Rosin Derivatives

The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier () were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d₉₀) ranged between 11–24 μm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size—small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n ～ 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.     

Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design

The present work aimed to synthesize solid lipid nanoparticles (SLNs) of Furosemide (FRSM). The parameter sensitivity analysis showed a significant effect of particle size and reference solubility on the AUC_0–∞, C_max and t_max. The FRSM-encapsulated SLNs were synthesized by the phase inversion temperature (PIT) technique using 3² factorial design. The optimal level of 221.28?mg of Compritol 888 ATO and 420?mg of Cremophor RH 40 showed a mean hydrodynamic diameter (MHD) of 25.54?±?0.57?nm, a polydispersity index (PdI) of 0.158?±?0.01, the % entrapment efficiency of 80.70?±?4.06%, percent dissolution efficiency of 71.72?±?1.52% and time elapsed for 50% drug release of 3.67?±?0.15?h. The PIT was determined using the turbidity method and the values ranged between 75°C and 73°C. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) images represent spherical to sub-spherical and smooth surface of SLN. The Fourier transform-infrared (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction (XRD) depict the drug-excipient compatibility. Korsmeyer–Peppas was found to be the best fit release kinetics model (R²?=?0.973; K-value?=?29.96 and release exponent?=?0.40), predicting the Fickian diffusion. The results advocate that the optimized formulation (OF) could promote the controlled release, and improve the physicochemical stability of the formulation. Hence, SLN could be a potential drug carrier for the peroral delivery of FRSM.     

Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties

Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al³⁺. The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2² randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32?μm and from 0.641 to 0.796?μm, respectively. The increase of polymer concentration (1–2%) and crosslinker concentration (3–5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.     

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.