Significant Enhancement In Solubility Research Articles

Exploring Deep Eutectic Solvents as Pharmaceutical Excipients: Enhancing the Solubility of Ibuprofen and Mefenamic Acid.

Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery.

Dipyridamole cocrystal tablets with enhanced solubility and dissolution at intestinal pH

The aim of the study was to prepare dipyridamole(DPM) cocrystals to alter itsphysicochemical properties as it ispoorly soluble in water, 6.8 pHbuffer and belongs to BCS class II. Cocrystals were prepared usingneat grinding method.
 Initial screening of cocrystals was done with melting point determination indicating formation of nine cocrystals. Based upon interference studies nine cocrystalswere finalized for solubility and dissolution studies. DPM-citric acid, DPM-hippuric acid, DPM-tartaric acid and DPM-oxalic acid cocrystalsshowed the significant enhancement in solubility and dissolution in 6.8 pH buffer.Further confirmation was done by DSC and PXRD studies. DPM-hippuric acid cocrystalshave shownpromising results for formation of cocrystals and considered for tablet formulation. DPM-hippuric acid cocrystal tablets were prepared by using various levels of carboxymethyl cellulose and microcrystalline cellulose. These tablets showed acceptable physical characteristics with subsequent rapid dissolution.

SOLUBILITY ENHANCEMENT OF RIVAROXABAN BY SOLID DISPERSION WITH POLYETHYLENE GLYCOL 4000

Objective: The aim of the work was to enhance the dissolution rate of rivaroxaban by preparing its solid dispersions (SDs) using hydrophilic carrier PEG 4000. Methods: The SDs of rivaroxaban with PEG 4000 were prepared at 1:1, 1:2 and 1:3 w/w ratios by physical mixing, melting and solvent evaporation techniques. The prepared solid dispersions were characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Both the solubility and dissolution rate of the drug in these formulations were increased. The used hydrophilic carriers showed a more than two-fold increase in dissolution rate in their prepared solid dispersions by melting or solvent evaporation techniques. The pure drug rivaroxaban as the pure drug shows a dissolution rate of nearly 39 % after 60 m, whereas the solid dispersions by melting or solvent evaporation showed 90% of dissolution after 60 m. The FTIR spectroscopic and DCS thermal studies showed the compatibility of rivaroxaban and the absence of well-defined drug polymer interactions, though the shift in peaks was observed due to the formation of new bonds. Conclusion: Formulation of solid dispersions of drug with hydrophilic carriers is a successful approach for solubility or dissolution rate enhancement of low soluble drug(s). In this work for solubility enhancement of rivaroxaban the hydrophilic carrier PEG 4000 showed significant solubility enhancement.

Valorization of spent fluorescent lamp waste glass powder as an activator for eco-efficient binder materials

• Use of spent fluorescent lamp waste glass was investigated. • Alternative activators were successfully synthesized using this waste glass. • These activators had similar effects to the commercial activator in producing AAM. • A recycling route for hazardous e-waste was preliminary demonstrated. Spent fluorescent lamp waste glass is considered hazardous and requires an appropriate management and recycling route. Due to its highly alkali-siliceous nature, the feasibility of using the powdered form of the fluorescent lamp waste glass (FGP) to synthesize an activator for activating the GGBS/FA blend was studied. Additionally, the solubility and reactivity of FGP were compared with waste beverage bottle glass powder (BGP). Results showed that FGP had a higher solubility and reactivity than BGP due to the presence of the higher network modifiers. A significant enhancement in solubility (about 19 %), total heat release (57 – 62 %), and compressive strength (85 – 89 %) was observed in FGP-based mixtures, implying its suitability for activator design. The mechanical and microstructural properties of the alkali-activated pastes (AAP) prepared with the FGP activators were similar to those prepared with the commercially sourced reference activator. Before activator preparation, washing FGP with water or acid enhanced the availability of soluble silicates. The activators prepared with those washed FGP accelerated the alkali-activation process and helped achieve better strengths for the corresponding AAP. Their 28-day compressive strength values were in the range of 36 – 40 MPa and comparable to the control (FGP-C). In addition, the microstructural analysis showed that the reaction products in these mixtures were of C-(N)-A S H gels type with high Si/Al and low Ca/Si ratios. Thus, a recycling route for spent fluorescent lamp waste glass was preliminary demonstrated in this study.

L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine.

The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via 1H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS’s utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil–water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release studies revealed that the prepared NPs could prolong GAL’s release for up to 12 days. In sum, regarding the most promising system, the results of the present study clearly suggest that the preparation of NPs using both Cys-CS and CDs results in a more thermodynamically stable drug dispersion, while a zero-order release profile was achieved, which is essential to attain a stable in vivo pharmacokinetic behavior.

A 32 Factorial Design Approach for Formulation and Optimization of Azilsartan Medoxomil Nanosuspension for Solubility Enhancement

Abstract: Background: Azilsartan medoxomil (AZL) is an orally active nonpeptide angiotensin II receptor antagonist with less water solubility and oral bioavailability. Objectives: Increase the solubility and dissolving rate of AZL. Materials and Methods: For formulation we used a probe sonication approach to create nanocrystals. The impacts of independent factors such as % polymer concentration (X1) and sonication duration (X2 min) on dependent variables such as particle size (Y1 nm) and % drug release (DR) were optimised using a 32 response surface methodology (Y2). Results: The prepared batches were examined for size, polydispersity index (PDI), zeta potential, solubility study and dissolution study. AZL nanocrystal (PS2 batch) particle size and zeta potential was found to be 168 ± 10 nm, 0.314 ± 0.02 and - 22.72 ± 2.6 mV respectively. The batch (PS2) with the best results was chosen and subjected to additional testing. In vitro dissolution of all 13 batches and pure drug was in ranges of 51.98-81.99% and 11.23 %, respectively. Conclusion: The FTIR analysis indicated that AZL and soluplus have no physical interaction. DSC, XRD, and SEM investigations revealed that the crystalline form of the medication was converted to an amorphous form, resulting in an improve water solubility and dissolution rate. Thus the studies exhibited nanocrystals prepared by probe sonication method showed significant enhancement in solubility and dissolution rate. Key words: Azilsartan medoxomil (AZL), Nanocrystal, Sonication, Solubility, Drug release.

Curcumin-loaded Hydrotropic Solid Dispersion Topical Gel Development and Evaluation: A Greener Approach Towards Transdermal Delivery of Drugs

Aims and Background: Curcumin's poor water solubility still presents a challenge. Because of Curcumin's instability in solubilizing solvents, using a non-sustainable solvent and dissolved oxygen in the solution might be the problem. Thus, considering all facts, looking for a promising alternative solvent medium is in need. Indeed, a solution of hydrotropic agent has been assessed recently. Hydrotropic agents are the best replacements for organic solvents. These are eco-friendly, safe, and non-toxic agents. Hence, the presented research focuses on improving the solubility of Curcumin through a hydrotropic solid dispersion approach. Amazingly, Curcumin showed a significant solubility enhancement in sodium salicylate hydrotropic Solution. Sodium salicylate hydrotrope ensured the stability of Curcumin in Solution, maintained homogeneity, and exhibited antioxidant properties. Hydrotropy combined with the solid dispersion technique is a simple and effective way to improve the bioavailability of Curcumin. Hydrotropic solid dispersion-loaded curcumin topical gel was developed to achieve transdermal delivery of Curcumin. Solid dispersion was prepared by solvent evaporation method and evaluated for in-vitro performance. Invitro drug dissolution, drug content, FTIR, and XRD were carried out for the prepared HSD. Objective: The selected HSD (1:4) was loaded into a topical gel by dispersion method, and in-vitro parameters like drug content, Spreadability, pH, rate of drug dissolution, and drug content were performed. Methods: The solubility study has substantially enhanced the solubility of Curcumin in a 2M sodium salicylate hydrotropic solution. Sodium salicylate was compatible with formulating the solid dispersion. Hydrotropic solid dispersion was successfully prepared in 1:4 ratios. XRD results have shown the amorphous nature of Curcumin in the presence of sodium benzoate. The dissolution studies have shown improved release compared to pure Curcumin and PM (1:4). The prepared HSD was then incorporated into a gel by dispersion method using carbopol 934 and hydroxypropyl methylcellulose as a gelling agent. The Cur-HSD gel was homogeneous and transparent in appearance. Result: The gel showed excellent Spreadability and drug content of 94.2 with 90.21% of percent drug release for 120 min and showed improved release in the presence of hydrotrope for improved topical delivery of Curcumin. Conclusion: Thus, to enhance the topical delivery of poorly soluble phytoconstituents, hydrotropes are suggested as a greener approach and to be applied for other poorly soluble phytoconstituents.

Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations

Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM–excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution.

Design, formulation and evaluation of multiparticulate time programmed system of ramipril for pulsed release: An approach in the management of early morning surge in blood pressure

The intent of the present study was to develop and evaluate multiparticulate pulsatile release system from the solid dispersion of ramipril to minimize the risk of cardiovascular events associated with early morning surge in blood pressure. Solid dispersion was prepared by solvent evaporation technique using β-cyclodextrin (β-CD) and polyvinyl alcohol (PVA) as carrier. In this study, the effect of PVA on β-CD solubilization of ramipril was investigated. The formulation was characterized by FTIR, DSC and X-ray diffraction analysis. Release rate indicated that addition of PVA showed significant enhancement of solubility of ramipril. The optimized formulation (SD5) showed 96±4.1% in 30 min and selected for the preparation of pulsatile release system. The system consisting of a core containing drug coated with an inner swelling layer of HPMC E5 and Ac-Di-Sol ® followed by an outer enteric coating layer of ethyl cellulose and Eudragit ® L100-55. It was observed that higher level of swelling layer enhanced the rapid release whereas higher level of polymeric layer enhanced the lag time but delayed the drug release. In vitro optimized formulation showed 7.42 ± 2.6% drug releases in first 5 h (lag time) followed by rapid drug release 96.55 ± 2.28% in 5 h. The in vivo data indicated that C max (3.81 μg/ml) and AUC (0-24) (7473.89 μg.h/ml) of optimized formulation was significantly increased (1.43 fold and 8.07 fold respectively) as compare to marketed tablet. Thus, the system can be a promising approach for the management of early morning surge in blood pressure with increased the solubility and bioavailability of ramipril.

Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines.

Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.

Improved Efficacy of Lovastatin from Soluplus-PEG Hybrid Polymer- Based Binary Dispersions

Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability. Objective: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions. Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches. Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group. Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.

Heteroaryl ether analogues of an antileishmanial 7-substituted 2-nitroimidazooxazine lead afford attenuated hERG risk: Invitro and invivo appraisal.

Previous investigation of the potent antileishmanial properties of antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines with biaryl side chains led to our development of a new clinical candidate for visceral leishmaniasis (DNDI-0690). Within a collaborative backup program, a racemic monoaryl lead (3) possessing comparable activity in mice but a greater hERG liability formed the starting point for our pursuit of efficacious second generation analogues having good solubility and safety. Asymmetric synthesis and appraisal of its enantiomers first established that chiral preferences for invivo efficacy were species dependent and that neither form afforded a reduced hERG risk. However, in line with our findings in a structurally related series, less lipophilic heteroaryl ethers provided significant solubility enhancements (up to 16-fold) and concomitantly attenuated hERG inhibition. One promising pyridine derivative (49) displayed 100% oral bioavailability in mice and delivered a 96% parasite burden reduction when dosed at 50mg/kg in a Leishmania donovani mouse model of visceral leishmaniasis.

Evaluation of Oleic Acid and Polyethylene Glycol Monomethyl Ether Conjugate (PEGylated Oleic Acid) as a Solubility Enhancer of Furosemide

Poor aqueous solubility limits the therapeutic efficacy of many marketed and investigational drugs. Synthesis of new drugs with improved solubility is challenging due to time constraint and expenses involved. Therefore, finding the solubility enhancers for existing drugs is an attractive and profitable strategy. In this study, PEGylated oleic acid (OA-mPEG5000), a conjugate of oleic acid and mPEG5000 was synthesized and evaluated as a solubilizer for furosemide. OA-mPEG5000 was evaluated as a nanocarrier for furosemide by formulating polymersomes. Solubility of furosemide in milli-Q water and aqueous OA-mPEG5000 solution was determined using shake flask method. At 37 °C, the solubility of furosemide in OA-mPEG5000 (1% w/w) and milli-Q water was 3404.7 ± 254.6 µg/mL and 1020.2 ± 40.9 µg/mL, respectively. Results showed there was a 3.34-fold increase in solubility of furosemide in OA-mPEG5000 compared to water at 37 °C. At 25 °C, there was a 3.31-fold increase in solubilization of furosemide in OA-mPEG5000 (1% w/w) (90.0 ± 1.45 µg/mL) compared to milli-Q water (27.2 ± 1.43 µg/mL). Size, polydispersity index and zeta potential of polymersomes ranged from 85–145.5 nm, 0.187–0.511 and −4.0–12.77 mV, respectively. In-vitro release study revealed a burst release (71%) within 1 h. Significant enhancement in solubility and formation of polymersomes suggested that OA-mPEG5000 could be a good solubilizer and nanocarrier for furosemide.

Improved Solubility of Itraconazole Binary Dispersions using Neem Gum: Development and Characterization of Topical Gel

Background: Itraconazole is a triazole derivative and possesses structural similarities to the azole group (imidazoles and triazoles). It is a broad spectrum fungistatic. It belongs to BCS class II category i.e. it has poor solubility and high permeability. Objective: Dissolution enhancement of poorly soluble itraconazole using purified neem gum as a natural carrier via binary dispersions and other methods was studied. Topical gel formulations of binary dispersions were developed and evaluated for in vitro and in vivo antifungal activity. Methods: Five batches of solid dispersions (SD1-SD5) in various ratios of drug: neem gum were prepared by the solvent evaporation technique. Other mixtures were also prepared by kneading, cogrinding, physical mixing methods and evaluated further. Topical gel formulations were further developed and evaluated for antifungal activity (both in vitro and in vivo). Results: Equilibrium solubility studies of various mixtures indicated SD3 (1:3) as the optimum batch out of all solid dispersion batches. Equilibrium solubility studies of mixtures (KM, CGM, PM, SM) indicated significant solubility enhancement of kneading mixture in comparison to other mixtures. FTIR studies indicated no interaction of the drug to the polymer. DSC, SEM and XRD studies indicated a transition from crystalline to the amorphous state of the drug. SD3 batch showed remarkably improved dissolution characteristics (100% drug release in 1.5 h) in comparison to the pure drug (38% in 2h). Further, the topical gel of SD3 was evaluated for in vitro diffusion, in vitro and in vivo antifungal activity. Sustained drug release (53% in 24 h) was observed in SD3 based gel formulation which is significantly higher than that in comparison to pure drug based gel (30% in 24 h). The increased area of zone of inhibition of SD3 based gel indicated better antifungal activity of the SD3 gel formulation. Further histopathology examination of skin specimens indicated enhanced efficacy of SD3 based gel in comparison to pure drug based gel. Conclusion: Solid dispersion based topical gel formulation exhibits better antifungal activity in comparison to pure drug based gel.

The influence of bromide-based ionic liquids on solubility of {LiBr (1) + water (2)} system. Experimental (solid + liquid) phase equilibrium data. Part 2

The main aim of the work is to investigate ionic liquids (ILs) or zwitterionic compound (ZI) as anti-crystallization additives for {LiBr (1) + water (2)} system, conventionally used as a working pair in absorption refrigeration technology. In this study, solubility of lithium bromide in water has been determined at wide temperature and composition range and compared to the literature data. The transition temperature and enthalpy between lithium dihydrate and lithium monohydrate forms were calculated using the van't Hoff plot. The main purpose of this work is to determine and discuss the solubility of lithium bromide in water in presence of IL, or ZI as an additive. The solubility measurements have been carried out using dynamic method within temperature range from (230 to 370) K. In this work, new ILs namely: N-methyl-N-(2-hydroxyethyl)morpholinium bromide, [MOR1,2OH][Br], N-(2-acetyloxy)ethyl-N-methyl-morpholinium bromide, [MOR1,2(OOC)1][Br], N-methyl-N-(2-ethoxy-2-oxoethyl)-morpholinium bromide, [MOR1,1(COO)2][Br], 1-methyl-3-(2-hydroxyethyl)imidazolium bromide, [Im1,2OH][Br], N-methyl-N-(2-hydroxyethyl)-pyrrolidinium bromide, [PYR1,2OH][Br], 2-hydroxyethypyridinium bromide, [Py2OH]Br], N-(2-hydroxy-ethyl)-N,N,N-triethyl-ammonium bromide, [N2,2,2,2OH][Br], N-(cyanomethyl)-N,N,Ntriethylammonium bromide, [N2,2,2,1CN][Br], N-(2-hydroxyethyl)-N,N-dimethyl-N-butyl-ammonium bromide, [N1,1,2OH,4][Br], N,N-di(2-hydroxyethyl)-N,N-dimethylammonium bromide, [N1,1,2OH,2OH][Br] and ZI namely: 3-(1-methylmorpholinium)propane-1-sulfonate, [MOR1,3SO3] were investigated. All compounds have been synthesized and characterized using NMR analysis. The thermophysical characterization of pure compounds, including: temperature of phase transition (Ttr), enthalpy of phase transition (∆trH), melting temperature (Tm) and enthalpy of melting (∆mH) have been measured using differential scanning calorimetry technique (DSC) at pressure p = 100 kPa. The experimental phase equilibria measurements for {LiBr (1) + IL, or ZI (2) + water (3)} ternary systems, with fixed IL to LiBr mass fraction w = 0.3 for all ILs and w = 0.1 and 0.2 for ammonium-based ILs and [MOR1,3SO3] have been performed by dynamic method. For all of the tested systems the transition point between lithium bromide dihydrate and monohydrate form was observed. Significant solubility enhancement of lithium bromide in water was obtained by adding ionic liquid, or zwitterionic compound to the lithium bromide + water solution. The experiment shows, that the greatest increase in solubility of LiBr in water was observed when [MOR1,3SO3], or [N1,1,2OH,2OH][Br] were added. This work is the first step of the experimental work in this area and further research will be carried out.

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates.

The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

Preparation and characterizations of stable amorphous solid solution of azithromycin by hot melt extrusion

In the present study aim was to prepare stable solid solution azithromycin dihydrate (AZI) by hot melt extrusion technology (HME). Soluplus and Kollidon® VA 64 were selected among polymers based on Hansen solubility parameter calculation in order to prepare amorphous of AZI. Further physicochemical properties of extrudates were characterized by DSC, FTIR, XRD, SEM and contact angle measurement. DSC revealed single broad endothermic peak in extrudates indicated miscibility of AZI into polymeric carriers, which formed monophasic solid system termed as solid solution. XRD confirmed amorphous nature of AZI in extrudates. DSC and XRD suggested molecular dispersion of AZI in polymeric carriers. Amorphous AZI exhibited statistically significant high solubility (P < 0.0001) in water in comparison with pure AZI. Solid solution batch AZI 03 showed significant enhancement in solubility (P = 0.0004) in pH 6. The dissolution in dissolution medium pH 6 and water resulted in statistically significant differences (P < 0.05) in the percentage amorphous AZI dissolved compared to the percentage AZI dissolved over the period of 60 min. Solid solution formulation showed better wettability than that of pure AZI. Amorphization and increased wettability attributed to solubility and dissolution rate enhancement. Assay and amorphous solid solution characteristics of AZI were found to be stable under accelerated storage condition as per ICH guideline for a period of six months. Therefore, hot melt extrusion technology was suitable method to prepare stable solid solution and dissolution rate enhancement for poorly soluble active like AZI.

Development of silk fibroin-derived nanofibrous drug delivery system in supercritical CO2

A silk fibroin (SF)-derived nanofibrous drug delivery system was fabricated by solution-enhanced dispersion via supercritical CO2 (SEDS) (20MPa pressure, 8mL/min flow rate, 35°C temperature) in this study. Curcumin (CM) was used as a water-insoluble drug model. Nanofibrous structure with controllable fiber diameter (<100nm) was obtained, and inter-molecular hydrogen bonds were formed between CM and SF; the crystallinity of the incorporated CM was remarkably decreased, which led to a significant enhancement in solubility of incorporated CM. In conclusion, SEDS could be developed to fabricate polymeric nanofibrous drug delivery system.

Celecoxib Bionanocomposite: Investigation of the effect of microwave irradiation using natural solubilizer

The main objective of present work was to enhance the solubility and improve the rate of dissolution of drug Celecoxib which is poorly water soluble as it belongs to BCS class II. Enhancement of solubility was be achieved by converting the BCS Class II drugs into bionanocomposites (BNCs) by using natural carriers and Microwave assisted Fusion method were employed, which ultimately leads to enhance the bioavailability of drug entity. Bionanocomposites (BNCs) were prepared using microwave assisted synthesis fusion method, where the drug entities were fused with natural carriers such as acacia, gelatin and ghatti gum. Selection of carriers was done based on their wetting and surfactant properties. The FTIR, DSC studies reveals that there was no any interaction between Celecoxib and Natural carriers. Solubility dissolution studies were carried out to investigate the solubilityenhancing property of the BNC. Mixture dissolution and in-vitro dissolution of prepared Celecoxib’s BNCs were characterized through DSC, SEM XRD and FTIR. From the study it was found that, the designed and developed nine batches of BNCs among which fourth batch was with Celecoxib: Acacia (1:4) shown the acceptable solubility i.e. 0.0113 mg/ml and its % drug release was found to be 91.58%. The four Batches of Immediate release tablet was prepared and evaluated using official methods viz; weight variation, Content uniformity, in-vitro dissolution. BNCs of Celecoxib prepared with Acacia provides significant enhancement in solubility and highlights its use in solubility and dissolution enhancement.

Controlling the size and morphology of griseofulvin nanoparticles using polymeric stabilizers by evaporation-assisted solvent–antisolvent interaction method

Griseofulvin (GF) is a potential drug for cancer therapy. However, its application is limited by its poor water solubility. Ultrafine GF nanoparticles were prepared through evaporation-assisted solvent–antisolvent interaction method for improving its solubility. Acetone was used as the solvent and water was used as the antisolvent. It was observed that particle size could be controlled by varying the concentration of GF in acetone. Average particle size was very low, 16 ± 4 and 28 ± 8 nm, when the concentration of GF was 5 and 25 mM, respectively, in acetone. However, the particle size increased drastically to more than 3 µm, when the concentration was increased to 50 mM. Interestingly, the presence of optimized concentration of polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) as stabilizers in the antisolvent resulted in significant reduction of particle size. Particle size decreased to less than 40 nm in the presence of the polymeric stabilizers, even when the concentration was 50 mM. Field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy imaging revealed that the polymeric stabilizers encapsulated very small GF particles and thus stabilized them. The solubility of GF-HPMC, GF-PVP, and the bare GF particles that were prepared from 50 mM solution (micro-GF) was nearly 24, 19, and 11 times, respectively, higher than that of raw-GF. In vitro dissolution studies revealed that almost 100 % of the drug was released in 60 min from GF-PVP and GF-HPMC. Fourier transform infrared spectroscopy did not detect any strong interaction between GF and the stabilizers. X-ray diffraction showed that the prepared GF nanoparticles and the micro-GF were in polymorphic form I. Differential scanning calorimetric studies showed that the crystallinity of the nanoformulated GF was only slightly lower than that of raw-GF. Thus, particle size reduction and the presence of stabilizers led to significant enhancement in solubility and dissolution rate.