Ternary Dispersions Research Articles

How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization

The purpose of this study is to improve the solubility and dissolution of a poorly soluble drug, Irbesartan, using solid dispersion techniques. For that purpose, different polymers such as Soluplus®, Kollidon® VA 64, Kolliphor® P 407, and Polyinylpyrrolidone (PVP-K30) were used as carriers at different concentrations to prepare solid dispersion formulations through the solvent evaporation method. In order to prepare binary dispersion formulations, Soluplus® and Kollidon® VA 64 were used at drug: polymer ratios of 1:1, 1:2, 1:3, and 1:4 (w/w). Saturation solubility of the drug in the presence of used carriers was performed to investigate the quantitative increase in solubility. Dissolution studies were performed to explore the drug release behavior from the prepared dispersions. Additionally, the characterization of the prepared formulations was carried out by performing DSC, SEM, XRD, and FTIR studies. The results revealed that among binary systems, K4 formulation (Drug: Kollidon® VA 64 at ratio of 1:4 w/w) exhibited optimal performance in terms of increased solubility, drug release, and other investigated parameters. Furthermore, ternary dispersion formulations of the optimized binary formulation were prepared with two more polymers, Kolliphor® P 407 and Polyvinylpyrrolidone (PVP-K30), at (Drug: Kollidon® VA 64:ternary polymer) ratios of 1:4:1, 1:4:2, and 1:4:3 (w/w). The results showed that KPVP (TD3) exhibited the highest increase in solubility, as well as dissolution rate, among ternary solid dispersion formulations. Results of solubility enhancement by ternary solid dispersion formulations were also supported by FTIR, DSC, XRD, and SEM analysis. Conclusively, it was found that the ternary solid dispersion-based systems were more effective compared to the binary combinations in improving solubility as well as dissolution of a poorly soluble drug (Irbesartan).

Research on Percolation Characteristics of a JANUS Nanoflooding Crude Oil System in Porous Media.

According to the research status of low-permeability reservoir development, in order to find an intelligent and efficient displacement method, a Janus smart nanocapsule (embedding nanomaterials with surfactant function into the polymer) is developed in this paper. There are two kinds of phase fluids in the migration of porous media, the initial Janus intelligent microcapsule slow-release liquid (dissolved and undissolved AP-g-PNIPAAM and Janus functional particle ternary dispersion) and the later AP-g-PNIPAAM and Janus functional particle binary dispersion. Comprehensively, using the indoor oil displacement experiment, the seepage characteristics of the Janus smart nanocapsule (JSNC) in porous media are studied, and their macro and micro oil displacement mechanisms are revealed. Research shows that Janus intelligent microcapsules have good mobility control ability in low-permeability heterogeneous reservoirs. The displacement performance of stepped differential pressure shows that the displacement medium can expand the swept volume. The research results presented can show that the JSNC oil displacement system has great application potential for the development of low-permeability reservoirs.

Physical Characterization and In Vitro Evaluation of Dissolution Rate from Cefpodoxime Proxetil Loaded Self Solidifying Solid SNEDDS.

Cefpodoxime Proxetil (CPD) is a broad-spectrum cephalosporin indicated in respiratory and urinary tract infections. CPD is a BCS class IV drug with pH-dependent solubility and has poor bioavailability. This study investigated the challenges of developing ternary components based on solid SNEDDS of CPD for in vitro dissolution rate enhancement and self-solidifying behaviour. Tween 80, Transcutol and PEG6000 were employed as surfactants, solvents and solidifiers for a base of ternary components to develop self-solidifying solid SNEDDS, respectively. Ternary phase diagrams were used to characterize solidifying behaviour of ternary components in different proportions. S-SNEDDS formulations were drawn on the solidification areas available in the phase diagram and characterized for IR, XRD, DSC and in vitro drug release in various pH media. Ternary components for the preparation of self-solidifying solid SNEDDS were selected based on drug solubility. FTIR and DSC characterization studies ruled out any drug interaction between CPD and components chosen to prepare S-SNEDDS. CPD was transformed from a crystalline into an amorphous state in ternary dispersions as revealed from XRD data. Optimized formulation (S-S 1) demonstrated more than 95% of drug release irrespective of the pH environments of the medium. Calculation of dissolution efficiency and similarity factors indicate that S SNEDDS resulted in a higher drug dissolution rate over binary dispersion (p<0.01). The stability studies showed that the S SNEDDS were stable in performances and CPD assay. The present investigation provides an alternative approach for enhancing the CPD dissolution rate using self-solidifying solid SNEDDS exhibited solidification behaviour at ambient temperature conditions and drug loading, which could be exploited over conventional dosage form.

Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug.

Optimization and evaluation of resveratrol amorphous solid dispersions with a novel polymeric system.

The preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, a single polymer often does not bring significantly enhance the solubility or amorphous stability of a poorly water-soluble drug. We found an application of a unique and novel binary polymeric blend in the preparation of solid dispersions. The main purpose of this study is to optimize and evaluate resveratrol (Res) amorphous solid dispersions with a novel polymeric system of poly (vinyl pyrrolidone) (PVP) and carboxymethyl chitosan (CMCS). The influence of three different release factors, the ratio of CMCS to the polymer mixture (CMCS% = X1), the ratio of Res to the polymer mixture (Res% = X2) and the surfactant (Tween 80 = X3), on the characteristics of released Res at various times (Q5 and Q30) was investigated. The computer optimization and contour plots were used to predict the levels of the independent variables as X1 = 0.17, X2 = 0.10 and X3 = 2.94 for maximized responses of Q5 and Q30. Fourier transform infrared spectroscopy (FTIR) results revealed that each polymer formed hydrogen bonds with Res. The solid performance and physical stability of the optimized ternary dispersions were studied with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), modulated differential scanning calorimetry (MDSC) and dissolution testing. SEM, XRD and MDSC analysis demonstrated that the Res was amorphous, and MDSC showed no evidence of phase separation during storage. Dissolution testing indicated a more than fourfold increase in the apparent solubility of the optimized ternary dispersions, which maintained high solubility after 90 days. In our research, we used CMCS as a new carrier in combination with PVP, which not only improved the in vitro dissolution of Res but also had better stability.

Development of the Binary and Ternary Atorvastatin Solid Dispersions: In Vitro and In Vivo Investigations.

The object of this study was to prepare binary and ternary solid dispersions of atorvastatin (ATR) by the melting method using PEGs and poloxamer 188 (P188) as the carriers, singly and in combination with each other. Dissolution behavior, solubility studies, X-ray diffractometry, differential scanning calorimetry, and Fourier transform infrared spectroscopy were studied. Furthermore, antihyperlipidemic activities of formulations were compared to each other by serum lipid analyses in hyperlipidemic rats. Based on the results, the highest dissolution efficiency (DE30 = 83%) was obtained by binary systems consisted of ATR and P188. Also, no additional improvement was observed in dissolution properties of ternary solid dispersion formulations. Solubility studies showed enhancement of ATR phase solubility in water and a buffer solution containing P188 or PEG 10000. Furthermore, saturated solubility of ATR in the buffer solution improved more than twofold in the optimized ternary dispersion system. No crystalline changes occurred in PEG-based formulations; meanwhile, partial amorphization happened in the ATR-P188 combination. Finally, the in vivo study in hyperlipidemic rats exhibited a rapid decrease in the lipid profile of all formulations compared to ATR (after 7 days). Moreover, reduction of serum triglycerides and total cholesterol on the 14th day in the ATR group (p value < 0.01) was less than solid dispersion or physical mixing preparations (p value < 0.001). These findings proved the appropriate influence of using PEG and P188 in solid dispersion systems for the improvement of the therapeutic efficiency of ATR.

Formulation and characterization of ternary amorphous solid dispersions of a highly potent anti-tubercular agent and curcumin

The enhancement of aqueous solubility of poorly water-soluble drugs is a challenge. Additional hurdle is to enhance the solubility of more than one drugs in same formulation for the combination therapy. This research paper presents the development of novel amorphous ternary (drug-drug-hydrophilic polymer) solid dispersions to simultaneously enhance the aqueous solubility and stability of two poorly soluble drugs. The ternary amorphous solid dispersions in the study contains the combination of a highly potent and novel anti-tubercular agent, Indole2-carboxamide derivative (North 2) and anti-oxidant, curcumin (CUR). Binary and ternary amorphous dispersions of North 2 and CUR were prepared using hydrophilic polymers, namely polyvinylpyrrolidone (PVP), Eudragit EPO® (EPO), and hydroxypropyl methylcellulose (HPMC), at 1:1 w/w (for binary solid dispersions) and at 1:1:2 w/w/w (for ternary solid dispersions) ratios. Differential scanning calorimetry (DSC) studies showed that North 2 has high crystallization tendency and formed an amorphous binary solid dispersion with only EPO, whereas CUR was characterized as low crystallization tendency compound and formed amorphous binary solid dispersions with EPO, PVP, and HPMC. All the three polymers formed amorphous ternary solid dispersions at 1:1:2 w/w/w ratios. Fourier transform infrared spectroscopy (FTIR) data showed significant peak shifts in both binary and ternary dispersions of North 2/CUR indicating molecular interactions. These interactions mainly involved the carbonyl group of both compounds, indole –NH of North 2 and phenolic –OH of CUR with the polymer chain. These interactions were confirmed by solution NMR and molecular modeling studies. In dissolution studies, out of the three hydrophilic polymers, EPO showed maximum solubility enhancement with and increased solubility by 55 and 59 times for North 2 and CUR, respectively, within 12 h. XRD stability data of the ternary solid dispersions showed that they were stable over 90 days at room temperature. The aqueous solubility of North 2 and curcumin was enhanced successfully with 50% loading of the drugs. Hence, this study shows the potential of designing ternary dispersions to achieve the solubility enhancement of a combination of poorly soluble drugs by utilizing a molecularly interacting hydrophilic polymer.

DEVELOPMENT OF AMORPHOUS BINARY AND TERNARY SOLID DISPERSIONS OF NATEGLINIDE FOR IMPROVED SOLUBILITY AND DISSOLUTION

Objective: Nateglinide is a commonly used oral hypoglycemic, biopharmaceutical classification system Class II drug, which shows relatively poor water solubility and variable bioavailability. The objective of the present investigation was to develop the binary and ternary solid dispersions of nateglinide for improved solubility and dissolution.&#x0D; Methods: Nateglinide solid dispersions were prepared by a common solvent evaporation method. Polymers like soluplus, kolliphor P188, sylloid 244FP, gelucire 48/16, affinisol (HPMCAS), HPβCD, βCD were used in different combinations. The physicochemical characterization of the optimized ternary dispersion was studied by using FT-IR, DSC, and PXRD. Solubility and dissolution behavior of all dispersions were studied.&#x0D; Result: From all prepared ternary solid dispersions, nateglinide dissolution was significantly faster than pure nateglinide. With ternary solid dispersion of NTG, soluplus and kolliphor P188 there was a big improvement in solubility and dissolution. This combination enhanced the solubility of NTG by 23 folds. Another ternary dispersion of NTG with soluplus and gelucire 48/16 enhanced solubility by 25 fold.&#x0D; Conclusion: Ternary solid dispersion found superior over binary dispersions. For the ternary dispersions, showing the best solubility, tablets were prepared. Dissolution and drug release from the formulated tablet was as good as a marketed product.

Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System.

The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms.

Investigation on preparation of poly (AM/SSS/AMPS) microspheres by dispersion polymerization system

The present work had the purpose of developing a class of terpolymer plugging microspheres for petroleum engineering. The terpolymer microspheres were prepared by dispersion copolymerization of acrylamide (AM), sodium 4-styrenesulfonate (SSS) and 2-acrylamido-2- methyl propane sulfonic acid (AMPS), using ethanol/deionized water as dispersion medium, polyvinyl pyrrolidone (PVP) as dispersant, N,N-methylenebisacrylamide (MBA) as crosslinking agent and potassium persulfate (KPS) as initiator. The influences of dispersion medium volume ratio, concentration of dispersant, pH value and stirring speed on the stability of dispersion system were investigated. The results showed that the stable dispersion system was obtained when ethanol-water ratio was 50:50 (v: v), the dispersant content was 15 wt. % (total mass of monomers), pH value was 7 and stirring speed was 200 r/min, which was suitable for ternary dispersion polymerization. FTIR spectrum and SEM images indicated the structure and surface morphology of microspheres.

Nocturnal pulse oximetry indicators in the evaluation of obstructive sleep apnea syndrome in outpatients with concomitant diseases of the upper respiratory tract and overweight

By using mathematical modeling, to evaluate the impact of upper respiratory tract diseases, retro- and micrognathia, and body mass index (BMI) on nocturnal pulse oximetry indicators (oxygen saturation level and oxygen desaturation index) in outpatients examined for suspected obstructive sleep apnea syndrome (OSAS). The study enrolled 260 subjects with a mean age of 47.8±12.0 years. All the examinees underwent outpatient pulse oximetry screening during nocturnal sleep because of suspected OSAS. Multislice spiral computed tomography was carried out to assess the paranasal sinuses and nasal septum. BMI was calculated. Variance factor analysis using an original programming application intended to create binary and ternary dispersion complexes was employed as a main mathematical tool. There were statistically significantly sets of risk factors for OSAS: nasal septum deviation + increased BMI + male gender = 68.66%; chronic allergic rhinitis + increased BMI + male gender = 63.09%; retromicrognathia + increased BMI + male ganger = 59.48%; and chronic tonsillitis + increased BMI + male gander = 60.88%. Higher BMI and male gender are a most statistically significant set of risk factors. Pulse oximetry screening during nocturnal sleep in snoring patients with suspected OSAS in combination with an assessment of age, sex, BMI, ENT comorbidity, retro- and micrognathia can predict the severity of the disease and serve as a basis for elaborating an OSAS screening program.

Impact of Eudragit EPO and hydroxypropyl methylcellulose on drug release rate, supersaturation, precipitation outcome and redissolution rate of indomethacin amorphous solid dispersions

The purpose of this work was to evaluate the impact of polymer(s) on the dissolution rate, supersaturation and precipitation of indomethacin amorphous solid dispersions (ASD), and to understand the link between precipitate characteristics and redissolution kinetics. The crystalline and amorphous solubilities of indomethacin were determined in the absence and presence of hydroxypropylmethyl cellulose (HPMC) and/or Eudragit ® EPO to establish relevant phase boundaries. At acidic pH, HPMC could maintain supersaturation of the drug by effectively inhibiting solution crystallization while EPO increased both the crystalline and amorphous solubility of the drug, but did not inhibit crystallization. The HPMC dispersion dissolved relatively slowly without undergoing crystallization while the supersaturation generated by rapid dissolution of the EPO ASD was short-lived due to crystallization. The crystals thus generated underwent rapid redissolution upon pH increase, dissolving faster than the reference crystalline material, and at a comparable rate to the amorphous HPMC dispersion. A ternary dispersion containing both EPO and HPMC dissolved rapidly, generating an apparent drug concentration that exceeded the amorphous solubility of indomethacin, leading to the formation of a new nanosized droplet phase. These nanodroplets dissolved virtually immediately when the pH was increased. In conclusion, the concentration-time profiles achieved from indomethacin ASD dissolution are a complex interplay of drug release rate, precipitation kinetics and outcome, and precipitate redissolution rate, whereby each of these processes is highly dependent on the polymer(s) employed in the formulation.

Clay-Alcohol-Water Dispersions: Anomalous Viscosity Changes Due to Network Formation of Clay Nanosheets Induced by Alcohol Clustering.

Clay-alcohol-water ternary dispersions were compared with alcohol-water binary mixtures in terms of viscosity and optical absorbance. Aqueous clay dispersions to which lower alcohols (ethanol, 1-propanol, 2-propanol, and tert-butanol) were added exhibited significant viscosity anomalies (maxima) when the alcohol content was 30-55 wt %, as well as optical absorbance anomalies (maxima). The maximum viscosity (ηmax) depended strongly on the clay content and varied between 300 and 8000 mPa·s, making it remarkably high compared with the viscosity anomalies (2 mPa·s) observed in alcohol-water binary mixtures. The alcohol content at ηmax decreased as the hydrophobicity of the alcohol increased. The ternary dispersions with viscosity anomalies exhibited thixotropic behaviors. The effects of other hydrophilic solvents (glycols) and other kinds of clays were also clarified. Based on these findings and the average particle size changes, the viscosity anomalies in the ternary dispersions were explained by alcohol-clustering-induced network formation of the clay nanosheets. It was estimated that 0.9, 1.7, and 2.5 H2O molecules per alcohol molecule were required to stabilize the ethanol, 2-propanol, and tert-butanol, respectively, in the clay-alcohol-water dispersions.

A Waterborne Coating System for Preparing Robust, Self‐healing, Superamphiphobic Surfaces

Existing coating systems for preparing superamphiphobic surfaces are predominantly confined to small‐scale uses due to the heavy use of organic solvents. Waterborne coating treatment is highly desirable for the high safety, low cost, and nonenvironmental impact, but it remains difficult to develop due to the problems in forming durable, homogeneous coating from an aqueous dispersion of amphiphobic substances. In this study, the authors have proved that lyophobic nanoparticles, fluorinated alkyl silane (FAS), and fluorocarbon surfactant can form a stable dispersion in water, suitable for preparing durable superamphiphobic surfaces on various solid substrates. A series of substrates including fabrics, sponge, wood, glass, and metal, after being coated with this ternary coating system, shows superamphiphobicity with low contact angle hysteresis. The coating is durable enough against physical abrasion, repeated washing, boiling in water, and strong acid/base attacks. Benefiting from FAS, the coating also has a self‐healing ability against both physical and chemical damages. The unexpected stability of the ternary dispersion is a result of the synergistic interaction of the three ingredients. Results from this study may promote the wide development of safe and cost‐efficient superamphiphobic techniques for diverse applications.

Colloid, adhesive and release properties of nanoparticular ternary complexes between cationic and anionic polysaccharides and basic proteins like bone morphogenetic protein BMP-2

Herein we describe an interfacial local drug delivery system for bone morphogenetic protein 2 (BMP-2) based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP). The application horizon is the functionalization of bone substituting materials (BSM) used for the therapy of systemic bone diseases. Nanoparticular ternary complexes of cationic and anionic polysaccharides and BMP-2 or two further model proteins, respectively, were prepared in dependence of the molar mixing ratio, pH value and of the cationic polysaccharide. As further proteins chymotrypsin (CHY) and papain (PAP) were selected, which served as model proteins for BMP-2 due to similar isoelectric points and molecular weights. As charged polysaccharides ethylenediamine modified cellulose (EDAC) and trimethylammonium modified cellulose (PQ10) were combined with cellulose sulphatesulfate (CS). Mixing diluted cationic and anionic polysaccharide and protein solutions according to a slight either anionic or cationic excess charge colloidal ternary dispersions formed, which were cast onto germanium model substrates by water evaporation. Dynamic light scattering (DLS) demonstrated, that these dispersions were colloidally stable for at least one week. Fourier Transform Infrared (FTIR) showed, that the cast protein loaded PEC NP coatings were irreversibly adhesive at the model substrate in contact to HEPES buffer and solely CHY, PAP and BMP-2 were released within long-term time scale. Advantageously, out of the three proteins BMP-2 showed the smallest initial burst and the slowest release kinetics and around 25% of the initial BMP-2 content were released within 14days. Released BMP-2 showed significant activity in the myoblast cells indicating the ability to regulate the formation of new bone. Therefore, BMP-2 loaded PEC NP are suggested as novel promising tool for the functionalization of BSM used for the therapy of systemic bone diseases.

Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib

The effectiveness of different polymers, alone or in combination, in inhibiting the crystallization of celecoxib (CEX) from amorphous solid dispersions (ASDs) exposed to different temperatures and relative humidities was evaluated. It was found that polyvinylpyrrolidone (PVP) and PVP-vinyl acetate formed stronger or more extensive hydrogen bonding with CEX than cellulose-based polymers. This, combined with their better effectiveness in raising the glass transition temperature (Tg) of the dispersions, provided better physical stabilization of amorphous CEX against crystallization in the absence of moisture when compared with dispersions formed with cellulose derivatives. In ternary dispersions containing 2 polymers, the physical stability was minimally impaired by the presence of a cellulose-based polymer when the major polymer present was PVP. On exposure to moisture, stability of the CEX ASDs was strongly affected by both the dispersion hygroscopicity and the strength of the intermolecular interactions. Binary and ternary ASDs containing PVP appeared to undergo partial amorphous–amorphous phase separation when exposed 94% relative humidity, followed by crystallization, whereas other binary ASDs crystallized directly without amorphous–amorphous phase separation.

Enhanced intracellular delivery of small molecules and drugs via non-covalent ternary dispersions of single-wall carbon nanotubes.

Albumins are used biologically and pharmacologically as transport proteins to deliver molecules to cells. Albumins also efficiently coat single-wall carbon nanotubes (SWCNTs) and promote their entry into mammalian and immune cells by the millions. Here, we show SWCNTs dispersed with bovine serum albumin (BSA) that are pre-loaded with rhodamine B (RB), small hydrophobic dye molecules that we consider here as models for drugs, drastically increase delivery of RB to HeLa cells and macrophages in culture. We determine spatial and concentration distribution of RB by independently visualizing SWCNTs and RB within the cells using unique SWCNT NIR fluorescence and fluorescence lifetime imaging of RB. The SWCNTs-BSA-RB ternary complexes are stable in water for days, and RB is only released when BSA is thermally or enzymatically denatured. We demonstrate efficacy of this approach by delivering daunomycin, a fluorescent chemotherapeutic drug that reduces proliferation in HeLa cells. Furthermore, we use molecular dynamics simulations to identify separate regions in BSA for drug loading and binding to SWCNTs. Together, our results demonstrate a pathway to enhance the delivery of a wide variety of drugs to cells through SWCNTs coated with albumin pre-loaded with drug molecules.

Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations.

The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations. The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions. Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization. Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization.

Development and evaluation of glibenclamide floating tablet with optimum release

Glibenclamide is a poorly soluble drug with narrow absorption window. The strategy of this work was to enhance the dissolution rate of Glibenclamide by solid dispersion (SD) technique with optimum formulation being developed as floating tablets. Binary SDs of drug and poloxamer 407 were prepared at different ratios. Ternary dispersion was prepared by the addition of sodium bicarbonate as third component. For floating tablets, a series of floating formulations was prepared using HPMC k4 (F1), HPMC k15 (F2) and combination of both with Carbopol (F3), using ternary solid dispersion as the drug matrix. Effect of matrix type was studied, F4 and F5 were prepared using the same floating matrix as F3 but drug was either binary poloxamer SD or physically mixed with bicarbonate. Unprocessed drug in floating matrix was used as control. All SDs increased drug dissolution rate, with ternary mixture showing the highest dissolution efficiency reflecting synergism between poloxamer and sodium bicarbonate. Solid state characterization showed evidences of decreased drug crystalline structure. F3 showed the best floating behavior. Considering floating behavior together with the release pattern, F3 was the optimum formulation. Overall, employing drug as ternary SD with optimum dissolution can provide flexibility in developing controlled release floating system.

Investigation of the interactions of enteric and hydrophilic polymers to enhance dissolution of griseofulvin following hot melt extrusion processing

This study focuses on the application of hot melt extrusion (HME) to produce solid dispersions containing griseofulvin (GF) and investigates the in-vitro dissolution performance of HME powders and resulting tablet compositions containing HME-processed dispersions. Binary, ternary and quaternary dispersions containing GF, enteric polymer (Eudragit L100-55 or AQOAT-LF) and/or vinyl pyrrolidone-based polymer (Plasdone K-12 povidone or S-630 copovidone) were processed by HME. Two plasticizers, triethyl citrate (TEC) and acetyl tributyl citrate (ATBC), were incorporated to aid in melt processing and to modify release of GF in neutral media following a pH-change in dissolution. Products were characterized for GF recovery, degrees of compositional amorphous character, intermolecular interactions and non-sink dissolution performance. Binary dispersions exhibited lower maximum observed concentration values and magnitudes of supersaturated GF in neutral media dissolution in comparison with the ternary dispersions. The quaternary HME products, 1 : 2 : 1 : 0.6 GF : L100-55 : S-630 : ATBC and GF : AQOAT-LF : K-12 : ATBC, were determined as the most optimal concentration-enhancing compositions due to increased hydrogen bonding of enteric functional groups with carbonyl/acetate groups of vinyl pyrrolidone-based polymers, reduced compositional crystallinity and presence of incorporated hydrophobic plasticizer. HME products containing combinations of concentration-enhancing polymers can supersaturate and sustain GF dissolution to greater magnitudes in neutral media following the pH-transition and be compressed into immediate-release tablets exhibiting similar dissolution profiles.