Concentration Of Poloxamer Research Articles

Injectable hydrogel scaffolds composed of Nanocellulose derived from sugarcane bagasse and combined with calcium for Bone regeneration

Injectable in-situ forming hydrogel scaffolds (IHS) were prepared using TEMPO-oxidized nanofibrillated cellulose (TONFC) originating from sugarcane bagasse. TONFC (0.5%w/w) was prepared and characterized, then various concentrations of poloxamer 407 (P407) were added to prepare the thermo-responsive hydrogels. Two sources of calcium; Fujicalin® (DCP) or Hydroxyapatite (TCP), were utilized to prepare the calcium-enriched HIS loaded with the antiresorptive drug raloxifene hydrochloride. Physicochemical evaluation comprising the gelation temperature, drug content, injectability and in-vitro drug release were performed in addition to the examination of the morphological characters. The chosen formulation 'Ca-IHS4' consisted of TONFC, 15% P407 and 10% TCP displayed the most extended release pattern (for 12 days) with the smallest burst effect. SEM images of the in-situ formed scaffolds presented a highly porous 3D structure essential for cells migration, nutrient transport and tissue infiltration. Cell biology studies were performed using Saos-2 cells and proved that “Ca-IHS4” is biocompatible and has cell regenerative effect. These findings suggest that Ca-IHS4 presents a simple, safe and non-invasive platform for bone regeneration.

Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug.

The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be -6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery.

Cubosome-based thermosensitive in situ gelling system for intranasal administration of lamotrigine with enhanced antiepileptic efficacy

Lamotrigine (LTG) is a second-generation antiepileptic drug that belongs to Biopharmaceutics Classification System (BCS) class II. LTG has a low probability of crossing the BBB if administered orally. This study was designed to fabricate LTG cubosomal dispersion that is further loaded in a thermosensitive in situ gel to increase nasal residence time and enhance drug absorption across the nasal mucosal membrane. LTG-loaded cubosomes exhibited an entrapment efficiency ranging from 24.83% to 60.13%, a particle size ranging from 116.2 to 197.6 nm, and a zeta potential ≤ −25.5 mV. The selected LTG-loaded cubosomal formulation was loaded in a thermosensitive in situ gel (cubogel) employing different concentrations of poloxamer 407. In vitro release study revealed sustained drug release from cubosomal and cubogel compared with free drug suspension. In vivo studies revealed enhanced antiepileptic efficacy of LTG cubogel and LTG cubosomes compared with free drug in rats with pilocarpine-induced epilepsy by stimulating the release of gamma-aminobutyric acid (GABA), total antioxidant capacity (TAC), and serotonin and by inhibiting the release of Ca2+, dopamine, acetylcholine (Ach), C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP). LTG cubogel exhibited superior activity over LTG cubosomes. These findings reveal that the developed cubosomal thermosensitive in situ gel can enhance the antiepileptic efficacy of LTG via the intranasal route.

Effect of Poloxamer Binding on the Elasticity and Toughness of Model Lipid Bilayers.

Poloxamers, also known by their trade name, Pluronics, are known to mitigate damage to cellular membranes. However, the mechanism underlying this protection is still unclear. We investigated the effect of poloxamer molar mass, hydrophobicity, and concentration on the mechanical properties of giant unilamellar vesicles, composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine, using micropipette aspiration (MPA). Properties including the membrane bending modulus (κ), stretching modulus (K), and toughness are reported. We found that poloxamers tend to decrease K, with an impact largely dictated by their membrane affinity, i.e., both a high molar mass and less hydrophilic poloxamers depress K at lower concentrations. However, a statistically significant effect on κ was not observed. Several poloxamers studied here showed evidence of membrane toughening. Additional pulsed-field gradient NMR measurements provided insight into how polymer binding affinity connects to the trends observed by MPA. This model study provides important insights into how poloxamers interact with lipid membranes to further understanding of how they protect cells from various types of stress. Furthermore, this information may prove useful for the modification of lipid vesicles for other applications, including use in drug delivery or as nanoreactors.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421–588 nm with PDI values 0.34–0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489–725 nm with PDI 0.34–0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%–91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%–90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

Formulation Variables Effect on Gelation Temperature of Nefopam Hydrochloride intranasal in Situ Gel (Conference Paper) #

Nefopam (N.F.) HCl is a non-narcotic centrally-acting, non-opioid benzoxazocine analgesic to relieve acute and chronic pain. It exhibits low bioavailability (about 36%) due to its first-pass degradation in the liver.
 Intranasal administration has been used as a new route for targeting active brain sites and enhancing the bioavailability of N.F. HCl bypassing hepatic metabolism.
 In situ gel of N.F. HCl was prepared by the cold method using different concentrations of Poloxamer 407, Poloxamer 188, HPMC K4M, Carbapol 934, and Hyaluronic acid polymers.
 The results show that identification tests are superimposed with references, solubility study shows that N.F. HCl is suitable to be administered intranasally; Compatibility studies reveal incompatibility of Nefopam HCl with HPMC K4M and Carbapol 934; meanwhile, no interaction with Methylcellulose and Hyaluronic acid.
 In conclusion, the obtained results revealed the incredible ability of the produced N.F. HCl intranasal in situ gel is intended to enhance drug bioavailability bypassing the metabolizing effect of the liver that N.F. HCl is facing when given orally.

Potentiating the solubility of BCS class II drug zaltoprofen using nanodispersion technology

The aim of this work was to formulate zaltoprofen (ZLT) loaded polyvinyl pyrrolidone K30 (PVP K30) nanodispersions to improve the solubility of ZLT. By varying the concentrations of PVP K30 and poloxamer 407 (1:1, 1:2, 2:1 and 2:2) different trials of ZLT nanodispersions were developed by solvent evaporation technique. The effects of formulation variables on the particle size, zeta potential, drug content, and encapsulation efficiency of ZLT loaded nanodispersions (ZLTNDs) were investigated. The average particle size, zeta potential, drug content and entrapment efficiency of ZLT nanodispersions (ZLTNDs-4) were 285.40 ± 16.41 nm, −19.06 ± 1.50 mV, 73.11 ± 0.16 mg, and 91.37 ± 0.22%, respectively. The spherical shape of the nanodispersion was verified by Transmission Electron Microscope (TEM) analysis. Further the developed formulation was characterized using Fourier Transform Infrared Spectroscopy and Differential scanning calorimetry (DSC) analysis. The in vitro release studies revealed maximum ZLT release 95.78 ± 0.85% compared to pure ZLT 36.47 ± 0.84%. The in vitro anti-inflammatory effect of pure ZLT, ZLTNDs-4 and standard drug (diclofenac sodium) was tested by protein denaturation assay, and the results exhibited superior anti-inflammatory activity of ZLTNDs-4 was 33.33 ± 1.00%). The anti- angiogenesis assay (CAM assay) results indicated that absence of vascular inhibition compared to pure ZLT. The results of the present work can be used to enhance the poorly aqueous soluble of ZLT and may be extended for other hydrophobic compounds, benefiting the pharmaceutical industries, etc.

Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 32 Factorial Design to Improve Solubility and In Vitro Bioavailability.

Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30® and Poloxamer 188® as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 32 full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X1) and stirring speed (rpm) (X2) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with -22.5 to -30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability.

Development and Optimization of Solid Lipid Nanoparticle Based Gel of Desoximetasone

Background: The present study enlightens to enhance the residence time and prolonged release of the desoximetasone by incorporating it into solid lipid nanoparticles (SLN), prepared by hot melt homogenization process. The desoximetasone loaded SLN were incorporated into gel for topical application. Materials and Methods: The preliminary trial batches were carried out by varying the concentration of Poloxamer 188 and lipid concentration. The prepared solid lipid nanoparticles were evaluated for particle size and % entrapment efficiency. From preliminary batches, the levels of Poloxamer 188, Glyceryl Monostearate and Homogenization speed were selected. Desoximetasone loaded SLN were optimized by box-behnken design by Design Expert 10.0.1.0 software. Results: Optimization was done to study influence of X1-amount of lipid, X2-surfactant concentration and X3-speed of homogenization on particle size(Y1), polydispersity index(Y2) and % entrapment efficiency(Y3). From overlay plot, 3.330 g (X1), 0.542 g (X2) and 20930 rpm (X3) were selected. It was observed that there was influence of independent variables over dependent variables. Transmission Electron Microscopy was performed to physically check prepared SLNs. It was observed that majority of SLNs were in the range of 150-200nm. Various parameters like pH, Spreadability, Viscosity, % drug release in 24 hrs of optimized batch was found to be 7.1 ±0.04, 40.99 ± 0. 32g.cm/sec, 10255 ± 18.78 cps, 90.89 ± 0.52% respectively. Accelerated Stability study revealed that there were no significant changes observed upon accelerated stability conditions. Conclusion: Prolonged release of desoximetasone was achieved by preparing desoximetasone loaded SLN based gel for topical application.

Investigation and Characterization of Factors Affecting Rheological Properties of Poloxamer-Based Thermo-Sensitive Hydrogel.

Poloxamers are negatively temperature-sensitive hydrogels and their hydrophilic groups interact with water molecules at lower temperatures (liquid phase) while their hydrophobic groups interact more strongly with increases in temperature causing gelation. To investigate the factors affecting the rheological properties of poloxamers, various parameters including different poloxamer P407 concentrations, poloxamers P407/P188 blending ratios and additives were examined. The results presented a clear trend of decreasing gelling temperature/time when P407 was at higher concentrations. Moreover, the addition of P188 enhanced the gelling temperature regardless of poloxamer concentration. Polysaccharides and their derivatives have been widely used as components of hydrogel and we found that alginic acid (AA) or carboxymethyl cellulose (CMC) reduced the gelling temperature of poloxamers. In addition, AA-containing poloxamer promoted cell proliferation and both AA -and CMC-containing poloxamer hydrogels reduced cell migration. This study investigated the intriguing characteristics of poloxamer-based hydrogel, providing useful information to compounding an ideal and desired thermo-sensitive hydrogel for further potential clinical applications such as development of sprayable anti-adhesive barrier, wound-healing dressings or injectable drug-delivery system for cartilage repair.

Combinatorial Approach of Thermosensitive Hydrogels and Solid Microneedles to Improve Transdermal Delivery of Valsartan: an In Vivo Proof of Concept Study.

Due to the limitations of oral administration of valsartan, in this study, we aimed to develop thermosensitive hydrogel for sustained transdermal delivery and improved bioavailability of valsartan, which was further improved using solid microneedles. The thermosensitive gel formula was made using Poloxamer 407 and Poloxamer 188 in various ratios. Valsartan thermosensitive gels were evaluated for their gelation temperature, pH values, drug content, spreadability, viscosity, rheological properties, in vitro drug release, in vitro permeation, and ex vivo permeation. Finally, in vivo study was conducted, compared to oral administration. The results presented the formulations showed required characteristic for transdermal administration with desired thermosensitive properties. Based on the permeation test with and without microneedles, it was found that the use of microneedles could affect the permeation of valsartan. Specifically, the increase of microneedles' needle length also increased valsartan permeation. The combination with the highest permeation was produced by 1.55mm MNs with the amount of drug permeated of 2.27 ± 0.01mg. Importantly, the transdermal delivery of valsartan using this combination approach could significantly improve the bioavailability of valsartan in in vivo study. The concentration of poloxamer was able to affect the properties of the hydrogels, and the use of solid microneedles improved the transdermal delivery of valsartan. In vivo studies showed the improvement of the bioavailability of valsartan compared to oral administration, showing the effectiveness of this combination approach.

Development of Besifloxacin HCL Loaded Ocular İn Situ Gels; In Vitro Characterization Study

Objective: The aim of this study is to develop in situ gel formulations containing besifloxacin hydrochloride are heat triggered, which are prepared by using different poloxomer and derivatives different polymers that will change the gelling temperature to increase corneal contact time, regulate drug release, improve ocular bioavailability and increase patient compliance increase mucoadhesion.
 Material and Method: Various concentrations of poloxamer 188 (P188) and poloxamer 407 (P407) were used to create the in situ forming gels. To increase the gel's capacity for bioadhesion, mucoadhesives such hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were included in the formulations. Drug release in vitro, sol-gel transition temperature, rheological behavior, pH, clarity, and mucoadhesion force were all assessed for the produced formulations. 
 Result and Discussion: The developed formulations' gelation temperatures ranged from 29 to 35°C. The preparations' viscosity and mucoadhesion force increased with increasing P407, HPMC, and HEC concentrations. Besifloxacin HCl forms in situ gel formulas with K1, K2, K3, and K6 suited for mucoadhesion characteristics, gelation temperature, and viscosity. These formulations exhibit pseudoplastic flow. Increasing polymer concentrations resulted in a reduction in the burst release of the formulations. However, at the end of 6 hours, drug release was finished in all formulations. The results show that in situ gels containing P407 and P188 show promise for besifloxacin HCl application

Balsam Poplar Buds: Extraction of Potential Phenolic Compounds with Polyethylene Glycol Aqueous Solution, Thermal Sterilization of Extracts and Challenges to Their Application in Topical Ocular Formulations.

Phenolic compounds of natural origin have been valued for their beneficial effects on health since ancient times. During our study, we performed the extraction of phenolic compounds from balsam poplar buds using different concentrations of aqueous polyethylene glycol 400 solvents (10–30% PEG400). The aqueous 30% PEG400 extract showed the best phenolic yield. The stability of the extract during autoclave sterilization was evaluated. The extract remained stable under heat sterilization. Ophthalmic formulations are formed using different concentrations (8–15%) of poloxamer 407 (P407) together with hydroxypropyl methylcellulose (0.3%), sodium carboxymethyl cellulose (0.3%) or hyaluronic acid (0.1%). Physicochemical parameters of the formulations remained significantly unchanged after sterilization. Formulations based on 12% P407 exhibited properties characteristic of in situ gels, the gelation point of the formulations was close to the temperature of the cornea. After evaluating the amount of released compounds, it was found that, as the concentration of polymers increases, the amount of released compounds decreases. Formulations based on 15% P407 released the least biologically active compounds. Sterilized formulations remained stable for 30 days.

Statistically developed docetaxel-laden mixed micelles for improved therapy of breast cancer

Docetaxel (DTX) has poor solubility, serious side effects, and multi-drug resistance (MDR) limiting its use in cancer treatment. Hence, the present study aimed to formulate and develop docetaxel mixed micelles (DTX MMs) for breast cancer treatment. DTX MMs were prepared from a mixture of docetaxel, TPGS, and Poloxamer 188 by using the solvent evaporation method. A 32 factorial design was applied to examine the combined effect of two formulation variables, each at 3 levels, and the 9 possible combinations of DTX MMs. The concentration of TPGS (X1) and concentration of Poloxamer 188 (X2) were independent variables. Whereas, particle size (Y1), and % entrapment efficiency (%EE) (Y2) were dependent variables. DTX MMs were evaluated for particle size analysis, TEM, %EE, in vitro drug release, %hemolysis, and stability study. DTX MMs composition (F6) was optimized based on particle size (143.2 nm), zeta potential (-7.5 mV) and %EE (81%). The TEM images showed spherical-shaped MMs. DTX MMs showed moderately higher IC50 value, indicating lower cytotoxicity when compared to plain DTX against MCF-7 cells. Docetaxel's sustained release from MMs decreased its exposure to normal tissue. Studies using IR, DSC, and P-XRD showed no significant incompatibility. DTX MMs would be a potential therapy for chemotherapy against breast cancer

Synthesis, Characterization and Antimicrobial Activity of Poloxamer‐Assisted Copper Nanoparticles: Investigating the Effects of Different Concentrations of Poloxamer 407

AbstractThe development of copper nanoparticles (CuNPs) with antimicrobial activities shows high potential for various clinical applications. We herein synthesized Poloxamer(P407)‐assisted CuNPs with improved oxidative stability using a simple process that included environment friendly Vitamin C (ascorbic acid) as a reducing agent and nontoxic P407 polymer as a stabilizing agent. To optimize the reducing agent, the effect of the molar ratio of ascorbic acid‐to‐Cu2+ salt was investigated through fluorescence measurements. The UV‐Visible spectrum presented that the inclusion of P407 improved the efficiency of CuNPs synthesis. In addition, DLS demonstrated that when the concentration of P407 was increased, the particle size of CuNPs was reduced. According to the XRD patterns, all the CuNPs are fcc‐structured and crystalline. The FE‐SEM and EDX images indicated the cubic morphology and the absence of any oxides of copper. The synthesized CuNPs have different particle sizes, showing strong antimicrobial activities against Gram‐negative and Gram‐positive bacteria as well as funguses. Our findings suggest that P407‐assisted CuNPs could be a new way to fight both human and plant pathogens.

Cubosomes for Enhancing Intestinal Absorption of Fexofenadine Hydrochloride: In situ and in vivo Investigation.

PurposeThe aim of this work was to probe cubosomes for enhanced intestinal absorption and oral bioavailability of poorly absorbable fexofenadine HCl (FEX-HCl).Materials and MethodsTwo cubosomal systems were fabricated utilizing glyceryl mono-oleate, a lyotropic mono lamellar lipid as oil phase and poloxamer407 as stabilizer at weight ratios of 8:2 and 7:3. The morphology of cubosomes was researched using transmission electron microscopy (TEM) and particle size was measured using photon correlation spectroscopy. FEX-HCl release was monitored in vitro. The effect of cubosomal encapsulation on intestinal absorption was assessed using in situ rabbit intestinal perfusion technique. Carrageenan induced rat paw edema model was utilized to monitor in vivo anti-inflammatory effect before and after cubosomal encapsulation.ResultsTEM revealed the existence of spherical and polygonal nanostructures arranged in honeycomb organization. Size measurement reflected nanoparticles with reduced size at higher poloxamer concentration. Release studies revealed liberation of FEX-HCl from cubosomes based on Higuchi kinetics model. The intestinal permeability data indicated incomplete absorption of FEX-HCl from simple aqueous solution with P-glycoprotein efflux contributing to this poor intestinal absorption. Incorporation of FEX-HCl in cubosomes enhanced membrane transport parameters. The intestinal absorption did not correlate with drug release suggesting that drug release is not the rate limiting with possible intact cubosomal transport. Cubosomal encapsulation of FEX-HCl significantly enhanced its in vivo anti-inflammatory efficacy compared to the aqueous FEX-HCl dispersion.ConclusionCubosomes are promising novel carriers for enhancing intestinal absorption of FEX-HCl. Intact FEX-HCl-cubosomal absorption is possible via trans-lymphatic pathway but this requires further investigations.

DEVELOPMENT OF NILOTINIB LOADED SOLID LIPID NANOPARTICLES AND OPTIMIZATION BY CENTRAL COMPOSITE DESIGN APPROACH

Objective: In current research, solid lipid nanoparticles (SLN) are formulated for the anticancer drug, nilotinib, to conquer the drawbacks associated with drug including low bioavailability and solubility. Methods: The formulation comprised of tripalmitin (lipid), poloxamer 188(surfactant) and glyceryl palmitostearate (cosurfactant) by solvent evaporation technique. The formulation and process variables of SLN were optimized by experimental design-Central composite design (CCD). The effect of drug to lipid ratio (A), concentration of Poloxamer 188 (B) and concentration of glyceryl palmitostearate(C), on particle size (Y1) and encapsulation efficiency (Y2) of SLN were evaluated. Three batches (F1-F3) of Nilotinib SLNs were formulated by desirability approach and evaluated. Results: The mean size of all the formulations ranged between 187–198 nm, PDI between 0. 291-0.652 and zeta potential between-21.8 to to-24.7 mV indicating the wide range of size distribution and stabiliity of the formulations. The total encapsulation efficiency of SLNs ranged between 85 to 86 %. The SEM analysis revealed the spherical shape of individual particles and PXRD results indicate amorphization of drug in SLN formulation. The drug release was continued for 24 h, indicative of controlled release drug delivery. Conclusion: From the above results it is concluded that the solubility and bioavailability of nilotinib is enhanced.

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine

Purpose Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. Methods The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit’s eye model. Results Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. Conclusion In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.

Fabrication and characterization of nanostructured lipid carrier system for effective delivery of poorly water-soluble drug quetiapine fumarate

The aim of present study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of quetiapine fumarate, a second-generation antipsychotic drug. Quetiapine Fumarate (QF) loaded NLC were prepared by hot homogenization followed by an ultrasonication method. Response surface methodology - central composite design (CCD) was used to systemically examine the influence of concentration of capmul MCM EP, concentration of poloxamer 188 and concentration of egg lecithin on particle size (PS) and % entrapment efficiency (% EE) and to optimize the NLC formulation. The CCD consists of three factored design with five levels, plus and minus alpha (axial points), plus and minus 1 (factorial points) and the centre point. A mathematical relationship between variables was created by using Design Expert software Version 12. The statistical evaluations revealed that three independent variables were the important factors that affected the PS and % EE of QF loaded NLC. The best fitted mathematical model was linear and quadratic for PS and % EE respectively. The optimized formulations found with 218.1±0.14nm of PS and 93±0.16% of % EE. Results illustrated the superiority of developed QF loaded NLC formulation as a stable drug delivery system, providing better bioavailability with the possibility of better treatment for psychological disorders.

Antimicrobial Activities of Propolis in Poloxamer Based Topical Gels.

Propolis contains a group of compounds with various activities. However, their low solubility is a drawback for the development of pharmaceutical formulations. In this study, poloxamers as a solubilizer and gelling agent were evaluated to develop a topical antimicrobial formulation of propolis. The effects of poloxamer type and concentration on the propolis solubility, release rate, and antimicrobial activities were investigated. Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans) were the representative bacteria and fungi, respectively. At 5%, poloxamer 407 (P407) and poloxamer 188 (P188) enhanced the propolis solubility by 2.86 and 2.06 folds, respectively; at 10%, they were 2.81 and 2.59 folds, respectively. The micelle size in the P188 formulation increased in the presence of propolis, whereas there was no change in the P407 formulation. Release rates of propolis decreased with the P188 concentration increase, which was attributed to viscosity increase. Both P188 and P407 formulations showed antimicrobial activity against S. aureus in a time-kill kinetics assay. However, only the P188 formulation reduced the cell’s numbers significantly against C. albicans, compared to the control. We speculate that P188 mixed micelles were more effective in releasing free active compounds to exhibit anti-microbial activity compared to the P407 micelles encapsulating the hydrophobic compounds in their cores. Propolis in P188 formulation is proposed as a potential topical antimicrobial agent based on its activity against both S. aureus and C. albicans.