Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation,cytotoxic, pharmacokinetic,and pathological evaluation

The cornerstone of this investigation is to determine the pharmacokinetic and histopathological behavior of solid lipid nanoparticles of capecitabine (CB-SLNs) in 1,2-dimethylhydrazine (DMH) induced colon cancer. The nanoparticles were prepared by microemulsion method. CB-SLNs were characterized for an optimal system. The cytotoxicity of CB-SLNs was evaluated by using MTT assay method. Further, pharmacokinetic and histopathological behavior of SLNs were studied in DMH induced colon cancer rats. The optimized nanoparticles have the particle size, zeta potential, and entrapment efficiency of 145.6?±?3.6?nm, ?26.9?±?2.7?mV, and 88.33?±?3.74%, respectively. Particles of CB were nearly spherical in shape and converted to amorphous form revealed by SEM and DSC, XRD studies. The nanoparticles showed dose-dependent cytotoxicity activity from 10 to 125?µg/mL compared with suspension. Pharmacokinetic studies revealed that 2.7-folds enhancement in the oral bioavailability and in aberrant crypt foci number, apoptotic index comparison with suspension formulation.     

Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization,in vitro characterization,cell line studies and in vivo efficacy in schizophrenia

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration.

Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies.

Results: The LH-SLNs had PS of 139.8?±?5.5?nm, EE of 79.10?±?2.50% and zeta potential of ?30.8?±?3.5?mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia.

Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.     

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.     

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation,design and in vivo evaluation

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56?±?8.57?nm, 0.27?±?0.028 and 83.66?±?5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p?0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.     

Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization,in vitro and in vivo evaluation

Purpose: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (～30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box–Behnken design (BBD) to improve the oral bioavailability.

Methods: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A₁), amount of surfactant (A₂) and concentration of co-surfactant (%) (A₃) were selected as independent variables, whereas, particle size (B₁), entrapment efficiency (B₂) and zeta potential (ZP, B₃) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.

Results: The optimized formulation with 132.89?mg of lipid, 106.7?mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9?±?3.7?nm of size, ?25.66?±?2.83?mV surface charge and 86.83?±?2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.

Conclusions: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.     

Development,optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box–Behnken experimental design

Objective: The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs).

Methods: Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett–Burman design (PBD) followed by Box–Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP.

Results: The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39?±?1.82?nm, apparent drug content (ADC) of 72.06?±?0.86%, and zeta potential (ZP) of ?13.91?±?1.21?mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48?h and followed Korsmeyer–Peppas release kinetic model.

Conclusions: A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.     

Preparation,characterization and in vitro anticancer activity of paclitaxel conjugated magnetic nanoparticles

In this study, magnetic nanoparticles (MNPs) coated with L-aspartic acid (F-Asp NPs) were synthesized through a co-precipitation method and conjugated with paclitaxel (PTX) (F-Asp-PTX NPs) by esterification reaction between the carboxylic acid end groups on MNPs surface and the hydroxyl groups of the PTX and studied its cytotoxic effect in vitro. The successful conjugating of PTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. The results showed that the average size was 46.11?±?7.8 (mean?±?SD (n?=?25)) nm. The cytotoxicity of void of PTX and F-Asp-PTX NPs were compared to each other by MTT assay of the treated MCF-7 cell line. The F-Asp-PTX NPs showed pH-dependent drug release behavior. These studies specify that F-Asp-PTX NPs have a very remarkable anticancer effect, for breast cancer cell line.     

Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design

Abstract

Objective: Nisoldipine (ND) is a potential antihypertensive drug with low oral bioavailability. The aim was to develop an optimal formulation of ND-loaded solid lipid nanoparticles (ND-SLNs) for improved oral bioavailability and pharmacodynamic effect by using a two-factor, three-level central composite design. Glyceryl trimyristate (Dynasan 114) and egg lecithin were selected as independent variables. Particle size (Y₁), PDI (Y₂) and entrapment efficiency (EE) (Y₃) of SLNs were selected as dependent response variables.

Methods: The ND-SLNs were prepared by hot homogenization followed by ultrasonication. The size, PDI, zeta potential, EE, assay, in vitro release and morphology of ND-SLNs were characterized. Further, the pharmacokinetic (PK) and pharmacodynamic behavior of ND-SLNs was evaluated in male Wistar rats.

Results: The optimal ND-SLN formulation had particle size of 104.4?±?2.13?nm, PDI of 0.241?±?0.02 and EE of 89.84?±?0.52%. The differential scanning calorimetry and X-ray diffraction analyses indicated that the drug incorporated into ND-SLNs was in amorphous form. The morphology of ND-SLNs was found to be nearly spherical by scanning electron microscopy. The optimized formulation was stable at refrigerated and room temperature for 3 months. PK studies showed that 2.17-fold increase in oral bioavailability when compared with a drug suspension. In pharmacodynamic studies, a significant reduction in the systolic blood pressure was observed, which sustained for a period of 36?h when compared with a controlled suspension.

Conclusion: Taken together, the results conclusively demonstrated that the developed optimal ND-SLNs caused significant enhancement in oral bioavailability along with pharmacodynamic effect.     

7-Ethyl-10-hydroxycamptothecin proliposomes with a novel preparation method: optimized formulation,characterization and in-vivo evaluation

Context:?The proliposomes were used to solve the stability of the ordinary liposomes. Objective: 7-ethyl-10-hydroxycamptothecin (SN-38) proliposomes for intravenous (i.v.) administration were prepared successfully by a new method.

Materials and methods:?SN-38 liposomes solution was reconstituting automatically from proliposomes on contact with the acetic acid buffer solution (0.2 M, pH 2.6). The formulation was optimized by the Box–Behnken design. The physicochemical characteristics of the SN-38 proliposomes were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The stability studies were also carried on. The FLU–HPLC system was served to study the concentration of SN-38 in the plasma of Sprague Dawley (SD) rats.

Results:?The optimized formulation was SN-38: 0.03 g; Soybean phospholipid (SP): 0.6 g; dextrose: 3.00 g. The entrapment efficiency of the optimized formulation was >85% and the mean particle size was about 231 nm. The stability studies showed that SN-38 proliposomes were stable in dark at 20–25°C for 6 months at least. The pharmacokinetic parameters of i.v. administration demonstrated that the half-life of SN-38 loaded in the liposomes was prolonged in vivo.

Discussion and conclusion:?The SN-38 proliposomes was prepared successful by the analysis of TEM, SEM, DSC and XRD, and SN-38 liposomes could be reconstituted on contact with the hydration medium. SN-38 liposomes circulated for a longer time in the blood circulating system than SN-38 solution, which contributed to maintaining the drug action.     

Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability

Context: The stabilization of flurbiprofen loaded poly-?-caprolactone nanoparticles (FB-P?CL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development.

Objective: Optimization of the FD to improve long-term stability of ocular administration’s FB-P?CL-NPs.

Methods: FB-P?CL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components.

Results: Optimized FB-P?CL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10?°C for 1?h, freezing at ?50?°C for 4?h, PD at +5?°C and 0.140 mbar for 24?h and a SD at +45?°C during 10?h. These conditions showed 188.4?±?1.3?nm, 0.087?±?0.014, 85.5?±?1.4%, 0.61?±?0.12%, ?16.4?±?0.1?mV and 325?±?7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD.

Conclusions: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.     

Development of a nanogel formulation for transdermal delivery of tenoxicam: a pharmacokinetic–pharmacodynamic modeling approach for quantitative prediction of skin absorption

This study investigates potentials of solid lipid nanoparticles (SLN)-based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetic–pharmacodynamic (PK–PD) modeling approach for predicting concentration–time profile in skin. A 2³ factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan-induced rat paw edema test. A published Hill model for in vitro inhibition of COX-2 enzyme was fitted to edema inhibition data. Concentration in skin was represented as a linear spline function and coefficients were estimated using non-linear regression. Uncertainty in predicted concentrations was assessed using Monte Carlo simulations. The optimized SLN was spherical vesicles (58.1?±?3.1?nm) with adequate entrapment efficiency (69.6?±?2.6%). The SLN-gel formulation was well-tolerated. It increased TNX activity and skin level by 40?±?13.5, and 227?±?116%, respectively. Average C_max and AUC_0–24 predicted by the model were 2- and 3.6-folds higher than the corresponding values computed using in vitro permeability data. SLN-gel is a safe and efficient carrier for TNX across skin in the treatment of inflammatory disorders. PK–PD modeling is a promising approach for indirect quantitation of skin deposition from PD activity data.     

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.     

Preparation,characterization and ex vivo–in vivo assessment of candesartan cilexetil nanocrystals via solid dispersion technique using an alkaline esterase activator carrier

The objective of this study was to improve candesartan cilexetil (CC) efficacy by formulating nanocrystals via solid dispersion (SD) technique using tromethamine (Tris). SD was prepared by solvent evaporation at different drug carrier ratios, evaluated for particle size, vitro dissolution studies, TEM, FTIR, and X-ray powder diffraction. Ex vivo, in vivo pharmacokinetic parameters were conducted on selected formulae compared to drug suspension and marketed product. Size analysis demonstrated formation of particles in the nanorange lower than 300?nm. A burst drug release followed by an improved dissolution was observed indicating instant formation of nanocrystals along with amorphization as confirmed by X-ray diffraction. FTIR studies suggested the absence of chemical interaction between Tris and CC. TEM revealed formation of irregular oval nanoparticles. SD-1:5 has higher apparent permeability coefficient compared to CC suspension. Furthermore, the pharmacokinetic results proved the ability of the formed nanoparticles to enhance the efficacy of CC compared to drug suspension and marketed product. In conclusion, using of Tris as alkaline esterase activator carrier could be a promising tool to bypass the controversial effect of esterase enzymes that may be a source for inter-individual variations affecting ester prodrug candidates’ efficacy.     

Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene

In the present work, MCM-41 and MCM-48 type of nanoparticles were successfully engineered. Effect of nanosize and amine functionalization on drug release, in vitro intestinal absorption and in vivo pharmacokinetic behavior was investigated in a comprehensive manner. The tailor-made bare and surface decorated MCM-41 and MCM-48 were synthesized and evaluated for their mesoporous skeleton, pore size, particle size, surface area, zeta potential, etc. by nitrogen sorption, DLS, TEM, etc. Incorporation of raloxifene (RLF) was affirmed using optimized immersion-solvent evaporation technique and its success confirmed by DSC, IR, and XRD analysis. TGA analysis revealed higher %grafting of amine groups on the exterior and larger RLF encapsulation into mesoporous derivate. The detailed in vitro release study revealed SGF to be the most compatible media for RLF showing an initial burst release from pristine nanoparticles and a delayed release from surface coated nanoparticles. Furthermore, release kinetics model data demonstrated Weibull and Higuchi as the best fit models for bare and amine-functionalized nanoparticles respectively. Moreover, an in vitro permeability study on Caco-2 cell line revealed higher absorption by engineered nanoparticle as compared to pure RLF and its marketed formulation. The supremacy in the in vivo pharmacokinetic parameters of RLF-41 and RLF-48 was demonstrated with 3.33 and 3.50 times enhancement in the bioavailability of RLF with respect to RLF suspension. To sum up, the results obtained were superior and promising for synthesized nanoparticles and more precisely for MCM-48 amongst them.     

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.     

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen

Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.

Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.

Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.

Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (C_max) of 9140.84?±?614.36?ng/ml at 3?h T_max and solid dispersion tablets showed C_max?=?11?445.46?±?149.23?ng/ml at 2?h T_max. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.

Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.     

Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: design,characterization, in vitro,ex vivo and in vivo appraisal

Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES₄) were found to be 137.9?nm and ?28.8?mV respectively. A maximum of 99.64?±?0.16% of ASM was released from SES₄ in 60?minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES₄ showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the t_max determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55?±?3.11% as extend of lymphatic absorption (r?=?0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.     

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.     

Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib

Objective: The present study discusses folic acid-etoricoxib-bovine serum albumin nanoparticles (F-ETX-NPs) using folic acid as an over expressed folate receptor ligand for activated macrophages in targeting of rheumatoid arthritis.

Materials and methods: For this purpose etoricoxib-loaded BSA nanoparticles (ETX-NPs) were prepared by desolvation method and activated folic acid conjugation with free amine group of BSA was confirmed by FTIR study and zeta potential measurements.

Results: The F-ETX-NPs showed spherical in shape with 215.8?±?3.2?nm average size?+?7.8?mV zeta potential, 72?±?1.3% etoricoxib entrapment efficiency and showed 93.1?±?2.2% cumulative etoricoxib release upto 72?h. The etoricoxib concentration from F-ETX-NPs was found to be 9.67?±?0.34?µg/g in inflamed joint after 24?h administration revealed remarkably targeting potential to the activated macrophages cells and keep at a high level during the experiment.

Discussion and conclusion: These results suggest that F-ETX-NPs are potentially vector for activated macrophages cells targeting of rheumatoid arthritis.