Formulation and evaluation of Gliclazide loaded nanoparticles for management of diabetes

Novel Self-Assembled Polycaprolactone–Lipid Hybrid Nanoparticles Enhance the Antibacterial Activity of Ciprofloxacin

Rational design of polysorbate 80 stabilized human serum albumin nanoparticles tailored for high drug loading and entrapment of irinotecan

Objectives: The purpose of present research work was to develop mucoadhesive microparticles of Zaleplon for nasal delivery with the aim to avoid hepatic first-pass metabolism, improve therapeutic efficacy and enhance residence time in the treatment of insomnia. Materials and Methods: Chitosan-based microparticles were prepared by the coacervation method by varying the drug:polymer ratio. The microparticles were evaluated for particle size and shape and surface morphology by scanning electron microscopy, drug content, drug entrapment efficiency, swelling study, in vitro mucoadhesion, differential scanning calorimetric (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR), in vitro drug release study, and ex vivo drug permeation. Results: Zaleplon microparticles showed irregular-shaped particles and particle size was found to be in the range of 4.97–10.6 μm, which is favorable for intranasal absorption. The prepared microparticles exhibited a good swelling index. The percentage drug content and entrapment efficiency was found to be in the range between 36.36% - 80% and 37.65% - 52.88%, respectively. In vitro mucoadhesion was performed by adhesion number using goat nasal mucosa and was observed in a range from 43.33 ± 4.409 to 75 ± 2.886%. It was observed that polymer concentration enhancement led to increased mucoadhesive strength. The results of DSC and XRD studies revealed the molecular amorphous dispersion of Zaleplon into the chitosan microparticles. IR spectra of Zaleplon along with excipient showed no interaction between Zaleplon and excipients. In vitro drug release from all the formulations was biphasic, being characterized by a slight “burst” followed by slow release. At the end of 12 h, F6 (1:6) showed drug release of 81.66 ± 1.545%, indicating sustained release. The permeation data of formulation from goat nasal mucosa was found near to that obtained with dialysis membrane in vitro. Conclusion: According to the obtained results, Zaleplon loaded chitosan microparticles prepared by coacervation method proved to be capable of sustained release and could be used through nasal route as an alternative to oral administration.

Solid lipid nanoparticles (SLNs) of piroxicam where produced by solvent emulsification diffusion method in a solvent saturated system. The SLNs where composed of tripamitin lipid, polyvinyl alcohol (PVAL) stabilizer, and solvent ethyl acetate. All the formulation were subjected to particle size analysis, zeta potential, drug entrapment efficiency, percent drug loading determination and in-vitro release studies. The SLNs formed were nano-size range with maximum entrapment efficiency. Formulation with 435nm in particle size and 85% drug entrapment was subjected to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for surface morphology, differential scanning calorimetry (DSC) for thermal analysis and short term stability studies. SEM and TEM confirm that the SLNs are nanometric size and circular in shape. The drug release behavior from SLNs suspension exhibited biphasic pattern with an initial burst and prolong release over 24 h.

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated.
 Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release.
 Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model.
 In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model.
 Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

<p>ABSTRACT<br />Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs<br />which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).<br />Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are<br />characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),<br />differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug<br />entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2<br /> factorial designs of<br />experiments by Design-Expert<br />®<br /> V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.<br />Results: The optimized batch had shown the entrapment efficiency of 98.10±0.24% and DL of 69.32±0.44% with particle size and zeta potential<br />as 344±5 nm and −42±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results<br />showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to<br />52.37±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.<br />Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,<br />and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing<br />conventional therapy in MDR-TB.<br />Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.<br />3</p>

Objective: This study aimed to enhance the solubility of voriconazole (VRZ) via loading to nanosuspensions using solvent/anti-solvent technique. The optimisation of independent variables (polymer concentrations) was carried out to achieve the desired particle size and maximise the percentage of entrapment efficiency (EE %) and drug loading (DL %) using design-expert®software. Methods: Design-Expert® software, version 13, was used to design and optimise nanosuspensions-loaded VRZ using 23 factorial designs. Concentrations of polyvinylpyrrolidone, hydroxypropyl methylcellulose and poloxamers were selected as independent variables to achieve ideal particle size, polydispersity index (PDI), entrapment efficacy (EE %) and drug loading (DL %). Atomic force microscopy (AFM), differential scanning calorimetry (DSC) and saturated solubility were used to assess the lyophilized nanoparticles. The compatibility between the drug and the polymers was studied using Fourier transform infrared spectroscopy (FTIR). Results: The particle size, PDI, EE %, and DL % were in the range of 15.6–145.6 nm, 0.010-0.120, 55.9 %-91.9 %, and 6.68-36.76 %, respectively. The saturated solubility of nanosuspensions-loaded VRZ (NS-VRZ) relative to free VRZ was increased tenfold in DW and twelvefold in PBS (pH 7.4). DSC thermogram confirmed the incorporation of VRZ in the nanosuspensions. The AFM of NS-VRZ validated spherical tiny particle size with a smooth surface. There is no chemical interaction between VRZ and the polymers, according to an FTIR investigation. Conclusion: The solubility of VRZ was successfully enhanced by loading to nanosuspensions. The solvent/anti-solvent technique was proven to be cost-effective, easy to operate and suitable for the preparation of NS-VRZ using Design-Expert®software.

Depression is a widespread psychiatric condition marked by ongoing sadness, disinterest, insomnia, and thoughts of self-harm. Fluoxetine HCl (FH) is a frequently prescribed antidepressant; however, it has low oral bioavailability (28%) due to significant first-pass metabolism and has side effects such as low blood pressure, gastrointestinal discomfort, and blurred vision. This research aimed to create and assess a novel intranasal nanostructured lipid carrier (NLC) system for FH, utilizing saffron oil (SO) as a functional lipid to enhance brain delivery while minimizing systemic side effects. FH-NLCs were prepared using the high-pressure homogenization and ultrasonication method and was optimized based on particle size, PDI, Drug loading and entrapment efficiency. The observed mean particle size of FH-NLCs is 117.3nm, PDI 0.219, and ZP -44.76mV which were ideal for nose-to-brain delivery. The optimized formulation showed high drug loading and entrapment efficiency. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed a uniform morphology, while X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated partial amorphization of the drug within the lipid matrix. The in vitro drug release exhibited a sustained profile without burst release, adhering to Korsmeyer-Peppas kinetics, which showed non-fickian diffusion Super Case II Transport (n = 1.14). Ex vivo permeation studies on goat nasal mucosa revealed significantly enhanced nasal mucosal permeability compared to the FH solution, indicating the permeation-enhancing properties of SO. Histopathological assessments confirmed the formulation's safety for nasal application. The pharmacodynamic evaluations demonstrated a synergistic antidepressant effect between FH and SO, thereby supporting improved therapeutic efficacy. The intranasal delivery of FH through SO-based NLCs offers a promising approach for direct brain targeting, potentially enhancing clinical outcomes in depression while reducing systemic side effects of FH.

Gemcitabine hydrochloride (Gem HCL) is a drug of choice for the treatment of most cancers, as a single or in combination chemotherapy. However, its bioavailability is a major concern because of its short half life and highly hydrophilic nature. To tackle this problem work has been planned to prepare solid lipid nanoparticles (SLN) of Gem HCL and analyzed them for drug carrying capacity and efficacy in vitro. The Gem HCL loaded nanoparticles (SLN) were prepared by microemulsion technique and optimized for drug carrying capacity, entrapment efficiency, stability, and effect of Gem HCL loaded SLN by MTT assay on human lung carcinoma cell lines (NCI-H522). SLN dispersion showed particle diameter ranging from 170 nm to 296 nm. The scanning electron microscopy (SEM) further confirmed the particle size of SLN. All SLN batches showed drug entrapment efficiency ranging from 29.6% to 65.66%. The results of differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that Gem HCL was dispersed in SLN in an amorphous state. The in vitro drug release study of the optimized formulation in phosphate buffer (pH 7.4) showed 56.73% of release of Gem HCL over a period of 24 hrs. Significant enhancement in the cytotoxic effect of Gem HCL loaded SLN, was noted compared to its liposome formulations. SLN mediated delivery can enhance the cytotoxic effects of Gem HCL compared to free drug and its liposomal formulation. Keywords: Solid lipid nanoparticles, Entrapment efficiency, Drug loading, Drug release, MTT assay, enhanced cytotoxicity, Gem HCL, Liposome, polymeric systems, SLN dispersion, Zeta potential, entrapment efficiency, ELISA, microemulsion, agglomeration

Due to poor bioavailability and chemical instability, the effectiveness of curcumin is negligible in the treatment of numerous diseases. Solid lipid nanoparticles (SLNs) increase the bioavailability of lipophilic compounds and protect the drug from gastrointestinal degradation. The objective of our study is the utilization of SLNs to improve the pharmacokinetics and pharmacodynamics of curcumin in the management of diabetes mellitus. Central composite design was used to prepare curcumin-loaded SLNs (Cur-SLN). The analysis of independent variables like drug concentration, lipid concentration, and surfactant concentration was carried out using analysis of variance (ANOVA) to obtain the optimized batch (optimized Cur-SLN) having the desired values of dependent variables particle size and entrapment efficiency. In vitro release, differential scanning calorimeter (DSC), transmission electron microscopy (TEM), and Fourier Transform Infra-Red (FTIR) studies of optimized Cur-SLN were carried out and then its pharmacokinetic and pharmacodynamic studies were performed. The model was found to be significant for particle size and entrapment efficiency based on F-value and p-value. The optimized batch's predicted values were in close agreement with the actual values of particle size and entrapment efficiency. TEM results confirm mono-dispersion and spherical shape of particles in the formulation. The DSC results confirmed the changing of drug from crystalline to amorphous form. Burst release followed by the sustained release was obtained in the in vitro release studies. The pharmacokinetic study shows enhanced bioavailability of optimized Cur-SLN compared with a plain drug suspension. The optimized Cur-SLN achieved higher antidiabetic activity in streptozotocin-induced diabetes mellitus rats than the plain drug suspension. SLNs can be used as a promising technique for delivering curcumin in the management of diabetes mellitus.

The purpose of this research was to study the effect of the lipid matrix on the entrapment of olanzapine (OL). OL-loaded solid lipid nanoparticles (SLNs) were prepared using lipids like glyceryl monostearate (GMS), Precirol ATO 5 (PRE), glyceryl tristearate (GTS), and Witepsol E85 (WE 85)--and poloxamer 407 and hydrogenated soya phosphatidylcholine as stabilizers--using a hot melt emulsification high-pressure homogenization technique, and then characterized by particle size analysis, zeta potential, differential scanning calorimetry (DSC), and powder X-ray diffraction (pXRD). Homogenization at 10,000 psi for 3 cycles resulted in the formation of SLNs with a mean particle size of approximately 190 nm for the 4 lipids investigated. The highest partition coefficient for OL between the melted lipid and pH 7.4 phosphate buffer (pH 7.4 PB) was obtained with GTS. The entrapment efficiency was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. DSC and pXRD showed that much of the incorporated fraction of OL existed in the amorphous state after incorporation into SLNs. A sharp increase in the flocculation of the SLN dispersions was observed upon addition of 0.6 M aqueous sodium sulfate solution. Nanoparticle surface hydrophobicity was in the following order: GTS SLNs > PRE SLNs > WE 85 SLNs > GMS SLNs. A significant increase in size and zeta potential was observed for GTS SLN and WE 85 SLN dispersions stored at 40 degrees C. Release of OL from the SLNs was sustained up to 48 hours in pH 7.4 PB and obeyed Higuchi's release kinetics.

The low-density lipoprotein (LDL) receptors overexpressed in brain capillary endothelial cell (BCEC) membrane were successfully targeted by polysorbate 80 (PS80)-coated polycaprolactone (PCL) nanoparticles for brain delivery of nevirapine (NVP). The nanoparticles prepared by emulsion solvent evaporation technique were evaluated for mean particle size (nm), zeta potential (mV), percentage drug entrapment efficiency (% EE), percentage drug loading (% DL), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), in vitro drug release study, stability study and in vivo biodistribution study. The mean particle size (nm) of uncoated nanoparticles, NvPNPs5, and PS80-coated nanoparticles, P80NvPNPs5, were (128.43 ± 4.82) nm and (218.3 ± 7.3) nm, respectively. The SEM and TEM analysis showed small-sized (< 100 nm), spherical-shaped, smooth-surface nanoparticles with less aggregation. The zeta potential (mV) analysis showed stable nanoparticles with values (− 72.1 ± 0.00) mV, NvPNPs5; (− 16.2 ± 0.00) mV, P80NvPNPs5; (− 16.2 ± 0.00) mV, 6CFNvPNPs5; and (− 13.6 ± 0.00) mV, P806CFNvPNPs5. The FT-IR and DSC report indicated drug excipient compatibility. P80NvPNPs5 showed an in vitro drug release for 36 h and its release kinetic was best fitted in Higuchi model (R2 = 0.936). Korsemeyer Peppas model showed an anomalous non-Fickian drug release mechanism as n = 0.767. P80NvPNPs5 released NVP for 24 h in the brain with prolonged blood circulation for 48 h as compared with NvPNPs5 and free drug suspension, (p < 0.05) in in vivo biodistribution study in Swiss Wistar rat. The confocal laser scanning microscopy (CLSM) study showed uniform distribution of P80NvPNPs5 in rat BCECs for 24 h post i.v. administration. The present observation concludes the futuristic scope of P80NvPNPs5 nanoparticles for brain delivery of different antiretroviral drugs as well as other CNS active drugs to treat several CNS disorders.

The design of effective drug delivery systems has recently become an integral part of the development of new medicines. Hence, research continuously keeps searching for ways to deliver drugs over an extended period of time with a well- ontrolled release profile.The ionotropic gelation method was used to prepare sweet potato starch-blended controlledc release alginate microbeads of ibuprofen. Sweet potato is an important crop in many developing countries. Although sweet potato originated from Central America, its ability to adapt to a wide variety of climatic conditions allows it to grow both in tropical and in moderate temperature regions of Africa, Asia and the Americas. The influence of various formulation factors such as in vitro drug release, entrapment efficiency, swelling study and micrometric properties was investigated. Other variables included sweet potato starch concentration, percentage drug loading, curing time, cross-linking agent and stirring speed during the microencapsulation process. The entrapment efficiencies were found in the range of 71.85 ± 2.04 - 94.53 ± 1.02%. The particle sizes were found in the range of 0.82 ± 0.006 - 1.08 ± 0.009 mm. This suggested that the ionotropic gelation method was successful in producing sweet potato starch-blended alginate microbeads.

Objective: The objective of this research was to formulate and evaluate olanzapine (OLE) mucoadhesive microsphere prepared using carbopol and sodium combination. OLE having extensive hepatic first pass metabolism and low bioavailability problem, determined the need for the development of sustained release formulation.Methods: OLE mucoadhesive microspheres were prepared by ionic gelation method. OLE mucoadhesive microspheres were prepared byionic gelation method by using calcium chloride as crosslinking agent. The OLE mucoadhesive microsphere was characterized by particle sizemeasurement, process yield, morphology of microsphere, drug entrapment efficiency, mucoadhesion test, differential scanning calorimetry, powder X-ray diffraction, Fourier transforms infrared (FTIR) study and in-vitro drug release.Results: The OLE mucoadhesive microsphere having mean particle size ranged from 546.0 µm to 554.3 µm, and the entrapment efficiencies ranged from 73% to 96%. All the olanzapine (OLE) microsphere batches showed good in-vitro mucoadhesive property ranging from 75.89% to 96.47% and in the in-vitro wash off test ranging from 68.12% to 81.3%. FTIR studies indicated the no drug-polymer interactions in the ideal formulation F9. Therewere no compatibility issues, and the crystallinity of OLE was found to be reduced shoeing less intense peak in prepared mucoadhesive microspheres, which were confirmed by differential scanning calorimeter and X-ray diffraction studies. Among different formulations, the OLE microspheres of batch F9 had shown the optimum percent drug entrapment of microspheres. Release pattern of OLE from F9 microspheres batch followed Higuchi kinetic model. Stability studies were carried out for F9 formulation at 4°C/ambient, 25±2°C/60±5%, 40±2°C/75±5% relative humidity revealed that the drug entrapment, mucoadhesive behavior, and drug release were within permissible limits.Conclusion: The results obtained in this work demonstrate the use of carbopol and sodium alginate polymer for preparation of mucoadhesive microsphere.Keywords: Ionic gelation method, Gastroretentive delivery, Mucoadhesive microsphere, Carbopol.

The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2–7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 32 factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50 mM exhibited best EE (82.12%), PS (196.71 nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.