Addition Of Hydrophilic Polymers Research Articles

Effect of Hydrophilic Polymers on Solubility Properties of Ketoprofen - 2,5-Dihydroxybenzoic Acid Multicomponent Solids

Ketoprofen is a medicinal compound derivative of phenyl alkanoic acid that works as an anti-inflammatory, antipyretic, and analgesic. In the Biopharmaceutical Classification Systems, ketoprofen is a class II drug with high permeability but low solubility. Due to its low solubility, the absorption and bioavailability of ketoprofen are very limited, which can affect its therapeutic effectiveness. This study aimed to increase ketoprofen's solubility by forming multicomponent solids using 2,5-dihydroxybenzoic acid coformer with adding hydrophilic polymers ((hydroxypropyl)methylcellulose, polyvinylpyrrolidone K90, and polyethylene glycol 4000). The results showed that ketoprofen with 2,5-dihydroxybenzoic acid coformer prepared using the solvent evaporation method formed a eutectic mixture. Adding hydrophilic polymers to the ketoprofen - 2,5-dihydroxybenzoic acid multicomponent solid increased the crystallinity and decreased the melting point of the multicomponent solids. The multicomponent solids of ketoprofen - 2,5-dihydroxybenzoic acid with the addition of hydrophilic polymers had solubility and dissolution efficiency significantly higher (p<0.05) than the ketoprofen - 2,5-dihydroxybenzoic acid multicomponent solids without hydrophilic polymers.

Formulation of mucoadhesive mouth paint for oral infections

Oral mucoadhesive mouth paint preparation was designed and prepared for the treatment of oral candidiasis, where prolonged drug release at the infected area is essential. Fluconazole, a recent triazole derivative having antifungal activity is chosen as the desired drug in this study to formulate mucoadhesive mouth paint. Oral candidiasis is a common infection in debilated patients, AIDS patients and in persons who administer immunosuppressive drugs. Mouth paints containing 1% fluconazole with hydrophilic polymer HPMC was prepared and compared with mouth paint prepared without the addition of hydrophilic polymer. The prepared mouth paint formulation was subjected to various evaluation parameters like pH determination, drug content, rheological behavior, mucoadhesive studies, spreadability and IR spectral analysis. In vitro drug release studies were carried out at salivary pH 6.4 using cellophane membrane as barrier. Stability studies were carried out at different temperature conditions like ambient temp (R. T.), 8 ± 1oC, 45 ± 2oC at 75% ± 5% R. H. (accelerated temperature) 3 months and analyzed at different time intervals for drug content, physical appearance, pH, mucoadhesive strength and spreadability and the prepared formulation was found to be stable. Antimicrobial studies were carried out to ascertain the antifungal activity of prepared mucoadhesive formulation against the pure drug. The test organism Candida albicans was a clinical isolate obtained from a diseased patient suffering from oral Candidiasis. In vitro antifungal activity was evaluated using standard Agar cup-plate method by zone inhibitions studies. Formulations, containing HPMC showed good zone inhibition. In vivo oral mucosal skin irritancy tests were carried out using mucoadhesive formulation on lab experimental animals (Rabbits and Guinea-pigs) and on healthy human volunteers. No edema, erythema, inflammation or redness in the mucosal cavity of both animals and human volunteers were observed.

Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization.

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Effect of Hydrophilic Polymers on Complexation Efficiency of Cyclodextrins in Enhancing Solubility and Release of Diflunisal.

The effects of three hydrophilic polymers, namely, carboxymethyl cellulose sodium (CMC-Na), polyvinyl alcohol (PVA) and poloxamer-188 (PXM-188) on the solubility and dissolution of diflunisal (DIF) in complexation with β-cyclodextrin (βCD) or hydroxypropyl β-cyclodextrin (HPβCD), were investigated. The kneading method was used at different drug to cyclodextrin weight ratios. Increases in solubility and drug release were observed with the DIF/βCD and DIF/HPβCD complexes. The addition of hydrophilic polymers at 2.5, 5.0 and 10.0% w/w markedly improved the complexation and solubilizing efficiency of βCD and HPβCD. Fourier-transform infrared (FTIR) showed that DIF was successfully included into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) confirmed stronger drug amorphization and entrapment in the molecular cage of cyclodextrins. The addition of PVA, CMC-Na or PXM-188 reduced further the intensity of the DIF endothermic peak. Most of the sharp and intense peaks of DIF disappeared with the addition of hydrophilic polymers. In conclusion, PXM-188 at a weight ratio of 10.0% w/w was the best candidate in enhancing the solubility, stability and release of DIF.

Structure and transport properties of polyvinyl chloride-based heterogeneous cation-exchange membrane modified by additive blending and sulfonation

In this work, the structure-performance relationship of modified heterogeneous ion-exchange membranes (IEMs) was investigated by the microheterogeneous model. Polyvinyl chloride (PVC)-based IEM has been modified by introducing hydrophilic additive and immersing in sulfuric acid solution. The modified membrane has displayed a high degree of structural heterogeneity with inter-gel phase fractions (f2) of 0.28 to 0.43. The α value isaround 0.20–0.31 which indicates that the prepared membranes have a randomly distributed conductive phase. In general, the inter-gel phase fraction (f2) has a positive effect on membrane conductivity. However, membrane permselectivity decreases at higher inter-gel phase fraction. The addition of hydrophilic polymer increases the fraction of inter-gel phase while the sulfuric acid immersion increases the gel-phase conductivity (kg). Moreover, it has been found that the permselectivity is linearly correlated to kg/f2.

Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

The number of poorly soluble new drugs is increasing and one of the effective ways to deliver such pharmaceutically active molecules is using hydrophilic polymers to form a solid dispersion. Bile salts play an important role in the solubilisation of poorly soluble compounds in the gastrointestinal tract (gut) prior to absorption. When a poorly water-soluble drug is delivered using a hydrophilic polymer based solid dispersion oral formulation, it is still unclear whether there are any polymer-bile salt interactions, which may influence the drug dissolution and solubilisation. This study, using two widely used hydrophilic model polymers, Hydroxypropyl methylcellulose (HPMC) and polyvynilpirrolidone (PVP), and sodium taurocholate (NaTC) as the model bile salt, aims to investigate the interactions between the polymers and bile salts in simulated fed state (FeSSIF) and fasted state (FaSSIF) gut fluids. The nature of the interactions was characterised using a range of NMR techniques. The results revealed that the aggregation behaviour of NaTC in FaSSIF and FeSSIF is much more complex than in water. The addition of hydrophilic polymers led to the occurrences of NaTC-HPMC and NaTC-PVP aggregation. For both systems, pH and ionic strength strongly influenced the aggregation behavior, while the ion type played a less significant role. The outcome of this study enriched the understanding of the aggregation behaviour of bile salts and typical hydrophilic pharmaceutical polymers in bio-relevant media. Due to the high surface-activity of the bile salts and their ability to interact with polymers, such aggregation behaviour is expected to play a role in drug solubilisation in the gut when the drug is delivered by hydrophilic polymer based dispersions.

Design and in vivo Evaluation of Gastro-retentive Floating Capsules of Amlodipine Besylate in Healthy Human Volunteers

The aim of this study was to explore the application of Gelucire 43/01 for the design of sustained release gastro retentive drug delivery system of Amlodipine besylate. Gelucire 43/01 has been used in floating sustained release formulations to prolong gastric residence time and increase its bioavailability. Gelucire 43/01 in combination with HPMC and Polyox was used as a release retarding polymer. HPMC of various viscosity grades HPMC K4M, HPMC K15M and HPMC K100M in combination of Gelucire were tested to obtain optimal total floating time as well as controlled drug release for prolonged period. Melt granulation technique has been used to prepare gastro retentive Amlodipine besylate formulations. All the formulations were evaluated in vitro for their floating ability and drug release. The floating times of all tablet formulations were greater than 12h. HPMC K4M in combination with Gelucire as polymeric matrix enhanced the drug release due to addition of hydrophilic polymer facilitated the swelling and erosion of the tablets. Incorporation of low viscosity polymer HPMC K100 M resulted in optimal floating as well as drug release for longer time. In vivo studies of optimized formulation show floating ability for 6 h in stomach. The results indicate that Gelucire 43/01 in combination with dissolution enhancers HPMC increase the permeability of the wax matrix, which provides improved dissolution thereby bioavailability of Amlodipine besylate and can be considered as a carrier for the development of sustained release floating drug delivery systems.

A Hetero-network Hydrogel With Self-assembled Nanofibers as Multiple-crosslinkers and Its Liquid-crystal-driven Healing Properties

Hetero-network hydrogels composed of hydrophilic polymers with terminal alkyl chains and nanofibrous self-assemblies were successfully fabricated. The gel formation was not observed in both cases of the self-assemblies in aqueous solution and hydrophilic polymer in aqueous solution. Furthermore the gel-to-liquid crystalline phase transition temperatures of nanofibrous self-assemblies were lowered by addition of hydrophilic polymers with terminal alkyl chains. From these observations, it was considered that the alkyl chains at polymer termini intercalated into the bilayer membrane-based nanofibrous self-assemblies to form cross-linking points. As far as we know, the hybrid hydrogel introduced in this communication is the first example of a hetero-network structure composed of supramolecular assemblies. When the hetero-network hydrogel was crushed by mechanical shearing, these hydrogels recovered by heating at temperatures above their gel-to-liquid crystalline transition temperatures.

Relationship between polymers compatibility and casting solution stability in fabricating PVDF/PVA membranes

Antifouling membranes are of great importance to the applications of membrane technologies for water and wastewater treatment. Blending with hydrophilic polymer to provide enhanced antifouling properties for polymeric membranes is regarded as a facile method, while in preparation process the compatibility of membrane materials and blending agents may cause changes in casting solution stability, thus significantly affecting the physicochemical properties of modified membranes. However, the relationship of membrane materials compatibility and casting solution stabilities remains unanswered. In this study, for the first time, the relations of polymers compatibility and casting solution stability are disclosed in fabricating poly(vinylidene fluoride)/poly(vinyl alcohol) (PVDF/PVA) membranes. Results showed that there existed a strong correlation of compatibility with solution stability, and that the increase of incompatibility between PVDF and PVA resulted in deterioration of casting solution stability as revealed by multiple light scattering spectroscopy (MLiSSP). The critical Turbiscan stability index (TSI) was determined to be 4.3 based on the nexus of compatibility-stability (the enthalpy≤10×10−3cal/mol); otherwise, a TSI value higher than 4.3 might cause the deterioration in properties of formed membrane. Casting solution with 0.1wt% PVA showed favorable stability and compatibility of blend polymers, and the formed membrane exhibited better intrinsic membrane properties and enhanced antifouling behavior. The obtained results highlight the nexus of compatibility-stability to be an important factor in fabricating polymeric membranes via addition of hydrophilic polymer.

Incorporation of Lamotrigine Drug in the PEO–PPO–PEO Triblock Copolymer (Pluronic F127) Micelles: Effect of Hydrophilic Polymers

AbstractThe hydrophobic drug Lamotrigine (LTG) shows low bioavailability after oral administration. Work has been performed to improve the aqueous solubility of LTG using the micelles of amphiphilic block copolymers. Polyethylene oxide‐ polypropylene oxide‐ polyethylene oxide triblock copolymers (PEO–PPO–PEO), known as Pluronic®, have been the subject of current interest due to the versatile structural possibilities of varying PEO/PPO ratios. Incorporation of LTG in the aqueous micellar solutions of Pluronic® F127 was investigated using UV–visible spectroscopy. The shapes and size of the micelles with and without LTG have been ascertained using dynamic light scattering and small angle neutron scattering experiments. Results show increase in the Pluronic® micellar size with hard sphere radius with the incorporation of LTG. The effect of hydrophilic polymers (PEG1500 and F68) on the LTG‐incorporated Pluronic® F127 micelles was also studied and found inefficient for enhancement of the solubility of LTG. Solid forms of LTG‐incorporated Pluronic® F127 micelles with and without hydrophilic polymers, coded as LPMs, were successfully prepared through the thin‐film hydration method. Fourier transform infrared spectroscopy, X‐ray diffraction spectroscopy and thermogravimetric analysis have been used to ensure the compatibility of the LTG with Pluronic® F127 micelles in prepared LPMs. All the LPMs showed good incorporation efficiency, loading capacity and the sustained release profile of LTG. Results showed no specific improvement with the addition of hydrophilic polymers in the studied concentration range.

Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin

In this study binary carbamazepine–hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine–hydroxypropyl-β-cyclodextrin–hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus® and two types of hydroxypropyl methylcellulose–Metolose® 90SH-100 and Metolose® 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine–hydroxypropyl-β-cyclodextrin–hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug–cyclodextrin–hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine–hydroxypropyl-β-cyclodextrin and ternary carbamazepine–hydroxypropyl-β-cyclodextrin–hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine–hydroxypropyl-β-cyclodextrin and ternary carbamazepine–hydroxypropyl-β-cyclodextrin–Soluplus® systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5min.

Development of anti-E6 pegylated lipoplexes for mucosal application in the context of cervical preneoplastic lesions

Cervical cancer induced by human papillomavirus (HPV) is the fourth highest mortality causing cancer in women despite the use of prophylactic vaccines. E6 targeting represents an attractive strategy to treat this cancer. Indeed, oncoprotein E6 is produced by keratinocytes infected by HPV and is partially responsible for carcinogenesis. E6 interferes with the apoptosis process in stressed cells by degradation of p53 tumor suppressor gene. Our strategy consists in using E6 siRNA complexed with pegylated lipoplexes. The addition of hydrophilic polymer around the nanoparticles is crucial to use them by vaginal application on account of cervicovaginal mucus. Physicochemical characteristics were evaluated and in vitro assays were performed to evaluate transfection potential, E6 mRNA extinction and p53 re-expression. Cationic liposomes DOTAP/Cholesterol/DOPE 1/0.75/0.5 (N/P 2.5) with or without 50% DSPE-PEG2000 and associated with siE6 have demonstrated good physicochemical characteristics in terms of complexation, size, surface charge and stability. Both lipoplexes have been tested on CaSki cell line (HPV 16+) with 50nM and 100nM of siE6. Lipoplexes formulations induce 30–40% of E6 mRNA extinction and induce the re-expression of p53. In conclusion, pegylated anti-E6 lipoplexes have demonstrated their efficiency to cross the cellular membrane and to release siRNA into the cytoplasm confirmed by final p53 protein production.

Effect of Temperature on Salt–Salt Aqueous Biphasic Systems: Manifestations of Upper Critical Solution Temperature

Water-miscible ionic liquids (ILs) may be salted out using kosmotropic salts such as potassium phosphate (K3PO4) to form salt–salt aqueous biphasic systems (ABS). The effect of temperature on these systems has been studied using phase diagrams and it is observed that the degree of binodal shift decreases (requiring lower IL and kosmotropic salt concentrations) with the increase of temperature following the trend [C4mim]Cl > [C4py]Cl > [C4mmim] Cl ~ [N4444]Cl. This trend can be correlated with the decreasing hydrogen bonding abilities of each salt. The phase behavior was also interpreted on the basis of critical solution temperature behavior of pure aqueous ionic liquid solutions. Additionally, the distribution of alcohols in these systems was studied as a function of temperature and it was found that the distribution ratios did not change with changes in temperature. The Gibbs energy of transfer of a methylene group in these systems and correlation to tie-line length was also determined. It was concluded that while the miscibility of alcohols increases in the ILs with increasing temperature, phase divergence in the aqueous biphasic system decreases, and thus these competing forces tend to cancel each other out for small polar molecules. A comparison is provided for the response to temperature in the currently studied salt–salt systems and analogous ABS formed by the addition of hydrophilic polymers to kosmotropic salts (polymer–salt) or other polymers (polymer–polymer).

Sustained release from hot-melt extruded matrices based on ethylene vinyl acetate and polyethylene oxide

The aim of the present study was to evaluate the importance of matrix flexibility of hot-melt extruded (HME) ethylene vinyl acetate (EVA) matrices (with vinyl acetate (VA) contents of 9%, 15%, 28% and 40%), through the addition of hydrophilic polymers with distinct swelling capacity. Polyethylene oxide (PEO 100K, 1M and 7M) was used as swelling agent and metoprolol tartrate (MPT) as model drug. The processability via HME and drug release profiles of EVA/MPT/PEO formulations were assessed. Solid state characteristics, porosity and polymer miscibility of EVA/PEO matrices were evaluated by means of DSC, X-ray tomography and Raman spectroscopy. The processability via HME varied according to the VA content: EVA 40 and 28 were extruded at 90°C, whereas higher viscosity EVA grades (EVA 15 and 9) required a minimum extrusion temperature of 110°C to obtain high-quality extrudates. Drug release from EVA matrices depended on the VA content, PEO molecular weight and PEO content, matrix porosity as well as pore size distribution. Interestingly, the interplay of PEO leaching, matrix swelling, water influx and changes in matrix porosity influenced drug release: EVA 40- and 28-based matrices extruded with PEO of higher MW accelerated drug release, whereas for EVA 15- and 9-based matrices, drug release slowed down. These differences were related to the distinct polymer flexibility imposed by the VA content (lower VA content presents higher crystallinity and less free movement of the amorphous segments resulting in a higher rigidity). In all cases, diffusional mass transport seems to play a major role, as demonstrated by mathematical modeling using an analytical solution of Fick’s second law. The bioavailability of EVA 40 and 28 matrices in dogs was not significantly different, independent of PEO 7M concentration.

Effect of hydrophilic polymers on isradipine complexation with hydroxypropyl β-cyclodextrin

Complexation of isradipine with hydroxypropyl β-cyclodextrin (HPβCD) in the presence and absence of 3 hydrophilic polymers—polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)—was investigated with an objective of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPβCD and on the dissolution rate of isradipine from the HPβCD complexes. The phase solubility studies indicated the formation of isradipine-HPβCD inclusion complexes at a 1:1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were quite stable. Addition of hydrophilic polymers markedly improved the complexation and solubilizing efficiencies of HPβCD. Solid inclusion complexes of isradipine-HPβCD were prepared in 1:1 and 1:2 ratios by the kneading method, with and without the addition of hydrophilic polymers. The solubility and dissolution rate of isradipine were significantly improved by complexation with HPβCD. The isradipine-HPβCD (1:2) inclusion complex yielded a 9.66-fold increase in the dissolution rate of isradipine. The addition of hydrophilic polymers also markedly improved the dissolution rate of isradipine from HPβCD complexes: a 11.72-, 17.01-, and 39.23-fold increase was observed with PVP, PEG, and HPMC respectively. X-ray diffractometry and differential scanning calorimetry indicated stronger drug amorphization and entrapment in HPβCD because of the combined action of HPβCD and the hydrophilic polymers.

An investigation into silk fibroin conformation in composite materials intended for drug delivery

Regenerated silk fibroin (SF) is a promising biomaterial to design drug delivery systems. To guarantee satisfactory prolonged release of loaded drugs, the native β-sheet conformation of SF is generally induced by a final curing which can determine instability of the loaded drug. This work aimed to investigate the influence on SF conformation of the addition of hydrophilic polymers, namely poloxamer 188 (PEO), a range of poly(ethylenglycol) (PEG)and poly(vinyl pyrrolidone) (PVP) and drying conditions, namely spray-drying or evaporation at 60 °C. DSC data on spray-dried products indicated that SF in composite materials was in the random coil conformation. ATR-FTIR spectroscopy with Fourier self-deconvolution of the amide I band revealed that SF in spray dried products was partially organized in the β-sheet structure only in presence of PEG4000. Both DSC and ATR-FTIR spectra registered on composite materials obtained by the slowest evaporation method indicated that all hydrophilic polymers favoured the β-sheet conformation. This feature was attributed to the formation of H-bonds with the tyrosine residues of the semicrystalline region in SF. In conclusion, this approach to prepare of SF/hydrophilic polymer composites at slow evaporation rate leads to water insoluble materials which could be used in the development of drug delivery systems.

Zero order drug delivery from double-layered porous films: release rate profiles from ethyl cellulose, hydroxypropyl cellulose and polyethylene glycol mixtures.

Abstract Laminated double-layered films comprising a drug-containing and drug-free layer were prepared using tripelennamine, barbitone, salicylic acid and caffeine dispersed in hydroxypropylcellulose (HPC) attached to ethyl cellulose (EC) films containing various proportions of polyethylene glycol (PEG) or HPC to enhance permeability. Drug release in vitro followed zero-order kinetics, rate constants being dependent on the thickness of the drug-free membrane, which was rate-controlling. Thickness-corrected zero order constants were independent of drug-loading, which did, however, control the duration of release. Permeability coefficient measurements on the same rate-controlling films used as single barrier membranes enabled the effective drug concentration (Co) at the interface between the laminated membranes to be estimated; Co was independent of drug loading and was of the order expected from the aqueous solubilities of the drugs. Release rates were enhanced by addition of hydrophilic polymer to the rate-controlling membranes, either linearly with fraction of additive for PEG to 0·6 or HPC to 0·4, or logarithmically for HPC from 0·4 to 0·8. Enhancement coefficients, which were different for each system, reflected the different mechanisms of hydrophilic polymer action. PEG was leached out rapidly, pores being formed in the matrix. In contrast, HPC was largely retained, so that the enhancement was less. The logarithmic enhancement stemmed from formation of swollen hydrated channels, which, unlike the low HPC fractions or the PEG systems, allowed entry of buffer ions, so that only in these channel systems were the release rates altered by change of the external pH.

Inlay osmotic pump tablets containing metformin and glipizide

The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-β-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G75% (75% GLZ release), tLMET (lag time of MET release from device), Q10 h (percent of MET released within 10 h), and RSQZERO (R2 of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.

Analysis of triclosan inclusion complexes with β-cyclodextrin and its water-soluble polymeric derivative

Interaction in solution and in the solid state of triclosan (TR), a practically water-insoluble antimicrobial agent, with parent β-cyclodextrin (βCD) and its water-soluble epichlorohydrin polymer (EPI-βCD) was investigated by several analytical techniques, to evaluate the role of the carrier features on the physicochemical properties of the drug–cyclodextrin complex. Phase-solubility studies showed the higher solubilizing and complexing ability of EPI-βCD ( K s = 11,733 M −1) than parent βCD ( K s = 2526 M −1). Actual inclusion complex formation between TR and both cyclodextrins tested was confirmed by 2D 1H NMR studies (ROESY), which also gave insight into some different drug/cyclodextrin binding modes between polymeric and parent βCD. Addition of hydrophilic polymers (hydroxypropylcellulose, hypromellose or amidated pectin) to TR/βCD systems increased βCD solubilizing efficacy, but, unexpectedly, decreased its complexing ability towards the drug. Solid binary and ternary samples prepared by co-grinding of components in high energy mills were carefully characterised by Differential Scanning Calorimetry, X-ray powder diffractometry and Fourier transform infrared spectroscopy. The results pointed out the higher affinity of EPI-βCD than βCD for the interaction with TR even in the solid state, resulting in the formation of completely amorphous products with superior dissolution properties. Addition of hydrophilic polymers failed to effectively promote solid-state interactions between TR and βCD, while their positive influence on drug solubility, observed in phase-solubility studies, was absent in solid TR/βCD/polymer products. Finally, the time–kill analysis, used to evaluate the TR antimicrobial activity against Streptococcus mutans, demonstrated the significantly ( p < 0.001) superior performance of both cyclodextrin complexes than drug alone, and confirmed the higher effectiveness ( p < 0.05) of TR/EPI-βCD than TR/βCD complex.

Confocal Microscopy and Competitive Adsorption: A New Look At Polymer-Enhanced Lung Surfactant Adsorption

Lung surfactant (LS) is a mixture of lipids and proteins that lines the air-liquid interface of the alveolar walls and modulates the surface tension in the lungs. It therefore greatly reduces the mechanical work of breathing as well as prevents alveolar collapse upon expiration. Blood serum leaking into the alveoli as a result of trauma can lead to LS inhibition, which is one characteristic of acute respiratory distress syndrome (ARDS). The competitive adsorption of serum proteins, such as albumin, to the air-liquid interface of the alveoli blocks LS from forming a functional monolayer during ARDS. The addition of hydrophilic polymers, such as polyethylene glycol and chitosan, to the liquid subphase has been shown to enhance interfacial LS adsorption in vitro. Optimal amounts of polymer allow LS to form a functional monolayer in the presence of albumin, thus reversing inhibition. Albumin must be displaced from the air-liquid interface in order for a functional monolayer of LS to form. Imaging of the competitive adsorption process with confocal microscopy has allowed us to better understand the mechanisms behind forming an interfacial LS monolayer under inhibitory conditions. We can simultaneously track LS, polymer, and albumin, as well as separately visualize phenomena occurring at the interface from those occurring in the bulk. As a result of these capabilities, we have studied how various parameters affect the transport of LS to the interface and the displacement of albumin in order to form a functional surfactant monolayer.