Lutrol F127 Research Articles

Formulation development and in vitro evaluation of solidified self-microemulsion in the form of tablet containing atorvastatin calcium

Aim: The objective of our present study was to prepare solid self-microemulsion in the form of tablet of a poorly water soluble drug, Atorvastatin calcium (ATNC) to increase the solubility, dissolution rate, and minimize the hazards experienced from liquid emulsions.Materials and methods: Self-microemulsifying ATNC tablet was formulated mainly by using self-emulsifying base, solidifying agent silicon dioxide and sodium starch glycolate as tablet disintegrant. Self-emulsifying base containing Transcutol P, Gelucire 44/14, and Lutrol F68 with their ratios in the formulation, were best selected by solubility study and ternary phase diagram in different vehicles. Particle size of microemulsion from tablet, physical parameters of the tablet and drug content has been checked. In vitro drug release rate has been carried out in phosphate buffer medium (pH 6.8). Physicochemical characterization of the drug in the optimized formulation has been performed to check drug-excipient incompatibility, if any.Results: Average particle diameter of the emulsions formed from the tablet was found to be below 100 nm in case of formulation F4 and F5, which indicated microemulsions has been formed. In vitro drug release from the formulations F3, F4, and F5 was found to be >90%, indicated the enhancement of solubility of ATNC compared to parent drug. Differential thermal analysis (DTA), Powder X-ray Diffraction (X-RD) and Fourier transform infra red (FTIR) study proved the identity of the drug in the optimized formulation.Conclusion: The tablet form of self-microemulsifying (SME) drug delivery is good for solubility enhancement.

Development And Characterization Of Atorvastatin Calcium Loaded chitosan Nanoparticles For Sustain Drug Delivery

The aim of this study is to formulate and characterize atorvastatin loaded chitosan loaded nanoparticles prepared by solvent evaporation method for sustained release. Low oral bioavailability of Atorvastatin calcium (14%) due to an extensive high first- pass effect makes it as prime target for oral sustained drug delivery. Weighed amount of drug and polymer were dissolved in suitable organic solvent DMSO and 2% acetic acid as an organic phase. This solution is added drop wise to aqueous solution of Lutrol F68 and homogenized at 25000rpm followed by magnetic stirring for 4hrs. Nanoparticles were evaluated for its particle size, scanning electron microscopy (SEM), Fourier-Transform infrared spectroscopy (FTIR), percentage yield, drug entrapment and for in vitro release kinetics. Among the four different ratios, 1:4 ratio showed high drug loading and encapsulation efficiency. SEM studies shows that prepared nanoparticles were spherical in shape with a smooth surface. Particle size of prepared nanoparticles was found to be in range between 142 nm to 221 nm. FTIR and DSC shows drug to polymer compatibility ruling out any interactions. In vitro release study showed that the drug release was sustained up to 7 days. Hence, prepared nanoparticles proved to be promising dosage form for sustained drug delivery of atorvastatin reducing dosing frequency, thus increasing the patient compliance. Copyright © 2012 VBRI press.

DNA nanotherapy for pre-neoplastic cervical lesions

ObjectiveThis study aims to test the hypothesis that targeted nanoparticle delivery of DNA encoding HPV16-regulated diphtheria toxin (DT-A) will result in the death of HPV16-infected cells. Materials and methodsPlasmid constructs containing a HPV16 Long Control Region (LCR) DNA sequence upstream of DT-A or luciferase reporter (Luc) DNA sequences were used to formulate poly(β-amino ester) nanoparticles. The effect on tumor growth of HPV/DT-A-nanoparticle injection directly into HPV16+ CaSki human cervical cancer cell-derived xenografts in mice was determined. To evaluate the ability of the HPV16 LCR regulatory sequence to activate gene expression specifically in HPV16-infected cells, mice underwent bioluminescent optical imaging following intraperitoneal injection of HPV/Luc-nanoparticles. The use of Lutrol F127, a thermal-sensitive gel, to target delivery of nanoparticles and subsequent gene expression to cervical epithelial cells was evaluated in ex vivo cultures of mouse cervix and following intravaginal delivery of nanoparticle/gel in mice, as well as in ex vivo cultures of surgical LEEP samples. ResultsThe selected HPV16 LCR regulatory sequence activates gene expression in both HPV16-infected cells and non-infected cells. However, in the cervix, it is specifically active in epithelial cells. Following exposure of cervical cells to HPV/DT-A-nanoparticles mixed with Lutrol F127 gel, DT-A is expressed and cells die. ConclusionsAn HPV16 DNA sequence that targets gene expression specifically to HPV16-infected cells remains to be discovered. Topical application of a Lutrol F127 thermal gel/nanoparticle mix is illustrative of how to restrict exposure of cells to therapeutic nanoparticles, thereby allowing for targeted DNA delivery to cervical pre-cancerous lesions.

Osmotic Pellet System Comprising Osmotic Core and In-Process Amorphized Drug in Polymer–Surfactant Layer for Controlled Delivery of Poorly Water-Soluble Drug

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs.

A potent preparation method combining neutralization with microfluidization for rebamipide nanosuspensions and its in vivo evaluation

Backgrounds: Rebamipide (REB) is classified as a Biopharmaceutics Classification System (BCS) Class-IV compound with poor aqueous solubility and poor permeability. The local concentration in the mucosa makes REB exhibiting the therapeutic activities, and the strategy of increasing the dissolution rate has the possibility to improve the oral gastrointestinal (GI) distribution when using REB nanosuspensions.Objective: The purpose of this work was to prepare REB nanosuspensions (REB-NSs) by combining neutralization with microfluidization to improve its dissolution rate and orally pharmacokinetic properties.Methods: The feasibility of using acid-base neutralization and microfluidization to prepare REB-NSs was studied, and the preparation was optimized by central composite design (CCD). Physical states were characterized by using some technical methods, while the plasma drug concentration and GI distribution in rodents were determined.Results: The experimental results identified a formulation with 10 mg/mL REB, 0.9% (w/v) Lutrol F127, and 0.6% (w/v) Kollidon 90F. The dissolution rate of the dried REB-NSs was faster than that of Mucosta® tablets in different media, and the pharmacokinetic study showed a slight increase (1.3-fold and 1.1-fold) in the AUC0–12 h compared with unprocessed conventional suspensions (CSs) and solutions. Also, the GI distribution of REB-NSs improved compared with REB-CSs, and this would be preferable to assist in protecting GI mucosa.Conclusion: The REB-NSs prepared by the combining method exhibited a higher plasma drug concentration and superior GI distribution, thereby demonstrating positive results for preparing nanosuspensions of local effective BCS IV drugs with pH dependence such as REB by this method.

Ciprofloxacin hydrochloride-loaded glyceryl monostearate nanoparticle: factorial design of Lutrol F68 and Phospholipon 90G

Purpose: This investigation was undertaken to develop glyceryl monostearate (Geleol)-based solid lipid nanoparticles (SLNs) of a hydrophilic drug ciprofloxacin HCl.Methods: Hansen's solubility parameter study was carried out in screening of a suitable carrier and solvent system. Subsequently, SLNs were prepared by solvent diffusion evaporation method and investigated for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug release behaviour.Results: Variations in SLN composition resulted in particle sizes between 170 and 810 nm and ZPs between 8 and 14 mV. The maximum EE was found to be 26.3% with particle size of 188.8 nm. SLN can sustain the release of drug for up to 15 h and it shows Higuchi matrix model as the best-fitted model. SLNs were stable without aggregation of particles under storage conditions.Conclusions: The results of this study provide the framework for further study involving the SLN formulation for hydrophilic drug molecule.

Characterization and antimicrobial activity of N-methyl-2-pyrrolidone-loaded ethylene oxide-propylene oxide block copolymer thermosensitive gel

The purpose of this study is to investigate the effects of N-methyl-2-pyrrolidone on the thermosensitive properties of aqueous ethylene oxide-propylene oxide block copolymer (Lutrol® F127) system. Due to the aqueous solubility enhancement and biocompatibility, N-methyl-2-pyrrolidone is an interesting solubilizer for the poorly water soluble drugs to be incorporated in the Lutrol® F127 system. Effect of N-methyl-2-pyrrolidone on physicochemical properties of Lutrol® F127 system was investigated using appearance, pH, gelation, gel melting temperature and rheology. The antimicrobial activity of the thermosensitive N-methyl-2-pyrrolidone gel was also tested. Lower N-methyl-2-pyrrolidone amount (≤30%w/w) could shift the sol-gel transition to a lower temperature but the gel-sol transition was shifted to a higher temperature. Higher N-methyl-2-pyrrolidone (≥40%w/w) could shift both sol-gel and gel-sol transitions of the system to a lower temperature. The amount of N-methyl-2-pyrrolidone >60% w/w could reverse the phase of the Lutrol® F127 system to non-newtonian flow at 4° and Newtonian flow at high temperature. Aqueous Lutrol® F127 system containing N-methyl-2-pyrrolidone exhibited antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans with the N-methyl-2-pyrrolidone in a dose-dependent manner.

Enhanced transdermal delivery of granisetron by using iontophoresis.

The purpose of the present study was to explore the passive and electrically assisted transdermal transport of Granisetron hydrochloride (GRA) in solution and gel formulation through iontophoresis and also the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting. In this study, iontophoretic permeation of GRA through guinea pig skin using silver-silver chloride electrode was performed and the effects of different variables on this phenomenon were evaluated. Preliminary in-vitro studies using aqueous GRA formulations investigating the effect of drug concentration (5, 10, 15 and 20 mg mL(-1)) on passive permeation, current density (0.2, 0.4 and 0.5 mA cm(-2)), mode of current application, penetration enhancers and effect of application duration were performed. As expected, GRA delivery was found to be increased with the elevation in drug concentration and current density. Anodal continuous current delivery was more effective in the permeation of GRA than the pulsed current method. Penetration enhancers were ineffective to show synergistic effect in conjunction with iontophoresis. It was evident that reservoir in the skin was not formed during the iontophoretic delivery. The results confirm that GRA is an excellent candidate for iontophoresis. The present study demonstrated the feasibility of GRA transdermal transport through the Lutrol F-127 gel by iontophoresis. Further in-vivo studies will be required to support in-vitro conclusions and develop in-vitro, in-vivo correlations.

Polymer-templated mesoporous carbons synthesized in the presence of nickel nanoparticles, nickel oxide nanoparticles, and nickel nitrate

Mesoporous carbon composites, containing nickel and nickel oxide nanoparticles, were obtained by soft-templating method. Samples were synthesized under acidic conditions using resorcinol and formaldehyde as carbon precursors, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock co-polymer Lutrol F127 as a soft template and nickel and nickel oxide nanoparticles, and nickel nitrate as metal precursors. In addition, a one set of samples was obtained by impregnation of mesoporous carbons with a nickel nitrate solution followed by further annealing at 400°C. Wide angle X-ray powder diffraction along with thermogravimetric analysis proved the presence of nickel nanoparticles in the final composites obtained using nickel and nickel oxide nanoparticles, and Ni(NO3)2 solution. Whereas, the impregnation of carbons with a nickel nitrate solution followed by annealing at 400°C resulted in needle-like nickel oxide nanoparticles present inside the composites’ pores. Low-temperature (−196°C) nitrogen physisorption, X-ray powder diffraction, and thermogravimetric analysis confirmed good adsorption and structural properties of the synthesized nickel–carbon composites, in particular, the samples possessed high surface areas (>600m2/g), large total pore volumes (>0.50cm3/g), and maxima of pore size distribution functions at circa 7nm. It was found that the composites were partially graphitized during carbonization process at 850°C. The samples are stable in an air environment below temperature of 500°C. All these features make the synthesized nickel–carbon composites attractive materials for adsorption, catalysis, energy storage, and environmental applications.

Nanonization of Itraconazole by High Pressure Homogenization: Stabilizer Optimization and Effect of Particle Size on Oral Absorption

This study was performed to optimize stabilizer systems used in itraconazole (ITZ) nanosuspensions to achieve the greatest extent of size reduction and investigate the effect of particle size on the in vitro dissolution and oral absorption of ITZ. The nanosuspensions were prepared by high pressure homogenization and characterized for particle size, zeta potential, and surface morphology. A central composite method was applied to identify a multiple stabilizer system of Lutrol F127 and sodium lauryl sulfate for optimal particle size reduction. By using the optimized system, an ITZ nanosuspension was prepared that showed the particle size results in good agreement with the values predicted by the model. The nanosuspension was physically stable at 25°C for 1 week. The crystalline form of ITZ was not altered. The ITZ dissolution rate is directly correlated to its particle size, and a smaller particle size yields a faster dissolution rate. Pharmacokinetics study was performed using four ITZ suspensions with various particle sizes in rats (n = 3). A significant increase in both maximal plasma concentration of drug and area under the drug concentration-time curve (AUC) was shown when the particle size was reduced from micrometer to nanometer. However, the AUC was not significantly affected by further reduction of the particle size within the nano-size range.

Formulation development and optimization of alpha ketoglutarate nanoparticles for cyanide poisoning

The purpose of this research work was to formulate and evaluate alpha ketoglutarate nanoparticles as dry powder inhaler for treatment of cyanide poisoning. Non-polymeric particles were prepared by nano-precipitation technique using various stabilizers. Selection of co-solvent and stabilizer was a key to produce stabilized particles. A combination of lutrol F68 and PVA as a crystal growth inhibitor seems to be best in achieving minimum particle size of 110.2 nm. On the basis of preliminary trials a Box–Behnken statistical design was employed to study the effect of independent variables, drug concentration ( X 1), stirring speed ( X 2), stirring time ( X 3), PVA concentration ( X 4), poloxomer concentration ( X 5) and volume of co-solvent ( X 6) on average particle size. Particle size varied from 110 to 875 nm depending upon the significant terms. Optimized formulation was predicted at drug concentration (50 μg/ml), stirring speed (640 rpm), stirring time (1 min), PVA concentration (1%), poloxomer concentration (1.69%) and volume of co-solvent (30 ml) with 104.6% experimental validity. The nanosized particles were further characterized by X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FT-IR) analysis. The results of particle characterization indicate that there was no physical disparity when compared with the commercial α-KG sample.

Strategies to improve dissolution and oral absorption of glimepiride tablets: solid dispersion versus micronization techniques

The objective of this study is to compare two different dissolution-enhancing strategies, solid dispersion (SD) and micronized techniques, for improving oral absorption of poorly soluble glimepiride, and to decide which strategy is suitable for its solubilization. The formulation of glimepiride SD was prepared by a solvent-evaporation process with povidone k-30 (PVPk30) at a weight ratio of 1:9 (drug:carrier). The other was prepared via a modified micronization technique, where glimepiride was premilled together with lactose and Lutrol F68 until the milled material passes through a 500 mesh ASTM sieve (30 μm). The dissolution results indicated that the two techniques were both capable of enhancing the dissolution rate and extent of glimepiride. The release profiles of the two prepared products were similar to the marketed product (Amaryl®) in various types of dissolution media. Furthermore, the oral bioavailability was evaluated for the three formulations in fasted beagle dogs. Statistical analysis indicated that there were no significant differences in pharmacokinetic parameters among the two prepared formulations and a marketed product, especially for AUC0–36, Cmax, and Tmax. The dissolution parameters (D10 and AUC0–20) in Tris buffer demonstrated the good in vitro/in vivo relationship with Tmax values for the three formulations. In conclusion, our studies confirmed that both SD and micronization techniques were capable of improving dissolution and oral absorption of glimepiride tablets to a similar extent as the marketed product, and the three glimepiride tablets were bioequivalent in the case of the rate and extent of absorption in dogs.

Mixed micellization between natural and synthetic block copolymers: β-casein and Lutrol F-127

Amphiphilic block copolymers and mixtures of amphiphiles find broad applications in numerous technologies, including pharma, food, cosmetic and detergency. Here we report on the interactions between a biological charged diblock copolymer, β-casein, and a synthetic uncharged triblock copolymer, Lutrol F-127 (EO(101)PO(56)EO(101)), on their mixed micellization characteristics and the micelles' structure and morphology. Isothermal titration calorimetry (ITC) experiments indicate that mixed micelles form when Lutrol is added to monomeric as well as to assembled β-casein. The main driving force for the mixed micellization is the hydrophobic interactions. Above β-casein CMC, strong perturbations caused by penetration of the hydrophobic oxypropylene sections of Lutrol into the protein micellar core lead to disintegration of the micelles and reformation of mixed Lutrol/β-casein micelles. The negative enthalpy of micelle formation (ΔH) and cooperativity increase with raising β-casein concentration in solution. ζ-potential measurements show that Lutrol interacts with the protein micelles to form mixed micelles even below its critical micellization temperature (CMT). They further indicate that Lutrol effectively masks the protein charges, probably by forming a coating layer of the ethyleneoxide rich chains. Small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM) indicate relatively small changes in the oblate micellar shape, but do show swelling along the small axis of β-casein micelles in the presence of Lutrol, thereby confirming the formation of mixed micelles.

Investigation of microemulsion system for transdermal delivery of itraconazole.

A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams. The optimized microemulsion was characterized for its morphology and particle size distribution. The optimized microemulsion was incorporated into polymeric gels of Lutrol F127, Xanthan gum, and Carbopol 934 for convenient application and evaluated for pH, drug content, viscosity, and spreadability. In vitro drug permeation of ME gels was determined across excised rat skins. Furthermore, in vitro antimycotic inhibitory activity of the gels was conducted using agar-cup method and Candida albicans as a test organism. The droplet size of the optimized microemulsion was found to be <100 nm. The optimized Lutrol F 127 ME gel showed pH in the range of 5.68±0.02 and spreadability of 5.75±1.396 gcm/s. The viscosity of ME gel was found to be 1805.535±542.4 mPa s. The permeation rate (flux) of ITZ from prepared ME gel was found to be 4.234 μg/cm/h. The release profile exhibited diffusion controlled mechanism of drug release from ME ITZ gel. The developed ME gels were nonirritant and there was no erythema or edema. The antifungal activity of ITZ showed the widest zone of inhibition with Lutrol F127 ME gel. These results indicate that the studied ME gel may be a promising vehicle for topical delivery of ITZ.

Soft-templating synthesis and adsorption properties of mesoporous carbons with embedded silver nanoparticles

Mesoporous carbons containing silver nanoparticles have been successfully synthesized under acidic conditions by employing resorcinol and formaldehyde as carbon precursors and triblock copolymer EO101PO56EO101 (Lutrol F127) as a soft template. Silver nanoparticles of ∼90 nm were added to the synthesis mixture to achieve 10 wt% and 20 wt% of Ag loading in the carbon. Also, tetraethyl orthosilicate (TEOS) was introduced to the system in order to improve adsorption properties of the silver-carbon composites and to reinforce its structure. The resulting carbons with incorporated silver nanoparticles featured high surface areas, large total pore volumes and primary mesopores in the range between ∼6–7 nm.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1–0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

Intravesical Toll‐like receptor 7 agonist R‐837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-beta-cyclodextrin (HPbetaCD). Induction of tumor necrosis factor alpha (TNFalpha) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFalpha and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPbetaCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFalpha and KC. Histological examination showed that poloxamer-HPbetaCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. The optimized poloxamer-HPbetaCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects.

Role of Zinc Oxide on Rheology of Thermosensitive Gel Developed for Periodontitis Treatment

Periodontal disease is a major cause of tooth loss, therefore a more recent approach such as thermosensitive gel is loaded with antimicrobial drugs to be delivered locally to the periodontal pocket. The effect of ZnO on thermosensitive gel properties including gelation-gel melting temperature, rheology, syringeability, and the release behavior of antimicrobial drug such as doxycycline hyclate were investigated. The increased amount of ZnO apparently decreased the gelation temperature of the Lutrol® F127 system. Syringeability of the doxycycline hyclate-Lutrol® F127 systems were increased with the increased amount of ZnO. System comprising zinc oxide could prolong the release of doxycycline hyclate from Lutrol F127 systems and could be delivered from a syringe through a needle for utilizing in periodontitis therapy at the periodontal pocket.

Characterisation of the thermal, spectroscopic and drug dissolution properties of mefenamic acid and polyoxyethylene–polyoxypropylene solid dispersions

The aim of this study was to investigate the solubility of mefenamic acid (MA), a highly cohesive, poorly water-soluble drug in a copolymer of polyoxyethylene–polyoxypropylene (Lutrol F68®), and to understand the effect drug polymer solubility has on in vitro dissolution of MA. Solid dispersions (SD) of MA were prepared by a hot melt method, using Lutrol F68® as a thermoplastic polymeric platform. High-speed differential scanning calorimetry (Hyper-DSC), Raman spectroscopy, powder X-ray diffractometry (PXRD) and hot-stage/fluorescence microscopy were used to assess the solubility of the drug in molten and solid polymer. Drug dissolution studies were subsequently conducted on single-phase solid solutions and biphasic SD using phosphate buffer pH 6.8 as dissolution media. Solubility investigations using Hyper-DSC, Raman spectroscopy and hot-stage microscopy suggested MA was soluble in molten Lutrol F68® up to a concentration of 35% (w/w). Conversely, the solubility in the solid-state matrix was limited to <15% (w/w); determined by Raman spectroscopy, PXRD and fluorescence microscopy. As expected the dissolution properties of MA were significantly influenced by the solubility of the drug in the polymer matrix. At a concentration of 10% (w/w) MA (a single phase solid solution) dissolution of MA in phosphate buffer 6.8 was rapid, whereas at a concentration of 50% (w/w) MA (biphasic SD) dissolution was significantly slower. This study has clearly demonstrated the complexity of drug–polymer binary blends and in particular defining the solubility of a drug within a polymeric platform. Moreover, this investigation has demonstrated the significant effect drug solubility within a polymeric matrix has upon the in vitro dissolution properties of solid polymer/drug binary blends. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4545–4556, 2009

Interactions in a nonionic surfactant and chitosan mixtures

Interactions in mixtures of nonionic surfactant, Lutrol F127, and cationic polyelectrolyte, chitosan from water solution and acetate buffer (pH 6.0 or 6.5 and ionic strength 0.1 and 0.5) have been investigated at two different temperatures (25 and 34 °C). Critical aggregation concentration (cac), critical micellization concentration (cmc) and the minimum area of Lutrol F127 molecule at the air/solution interface ( a), were determined using the surface tension measurements. The addition of chitosan to Lutrol F127 solutions shifted the cac and cmc to higher values; the effects were more pronounced for the cmc and in acetate buffer. The Lutrol F127 adsorption at the air/solution interface strongly depended on the equilibria in the bulk-phase, i.e. on the extent of the protonation of chitosan amino groups. The results were discussed in terms of electrostatic, hydrophobic and intra- and inter-polymer interactions.