Aqueous Solubility Of Drug Research Articles

Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development.

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed.

Significance of Polymers with "Allyl" Functionality in Biomedicine: An Emerging Class of Functional Polymers.

In recent years, polymer-based advanced drug delivery and tissue engineering have grown and expanded steadily. At present, most of the polymeric research has focused on improving existing polymers or developing new biomaterials with tunable properties. Polymers with free functional groups offer the diverse characteristics needed for optimal tissue regeneration and controlled drug delivery. Allyl-terminated polymers, characterized by the presence of a double bond, are a unique class of polymers. These polymers allow the insertion of a broad diversity of architectures and functionalities via different chemical reactions. In this review article, we shed light on various synthesis methodologies utilized for generating allyl-terminated polymers, macromonomers, and polymer precursors, as well as their post-synthesis modifications. In addition, the biomedical applications of these polymers reported in the literature, such as targeted and controlled drug delivery, improvement i aqueous solubility and stability of drugs, tissue engineering, and antimicrobial coatings, are summarized.

Sulfobutylation of Beta-Cyclodextrin Enhances the Complex Formation with Mitragynine: An NMR and Chiroptical Study

Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ11 = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.

Influence of choline-based ionic liquids as neoteric green solvents on aqueous solubility of lamotrigine and piroxicam drugs

Background: The low aqueous solubility of three important drugs (betamethasone (BETA), meloxicam (MEL) and piroxicam (PIR)) have been increased by use of deep eutectic solvents (DESs) based choline chloride/urea (ChCl/U), choline chloride/ethylene glycol (ChCl/EG) and choline chloride/glycerol (ChCl/G) as new class of solvents at T = (298.15 to 313.15) K. Methods: DESs were prepared by combination of the ChCl/EG, U and G with the molar ratios: 1:2. The solubility of drugs in the aqueous DESs solutions was measured at different temperatures with shake flask method. Results: The solubility of the investigated drugs increased with increasing the weight fraction of DESs. The solubility data were correlated by e-NRTL and Wilson models. Also, the thermodynamic functions, Gibbs energy, enthalpy, and entropy of dissolution were calculated. Conclusion: At the same composition of co-solvents and temperature, the BETA, PIR and MEL solubility was highest in (ChCl/U + water), (ChCl/U + water) and (ChCl/EG + water) respectively. The calculated solubility based on these models was in good agreement with the experimental values. In addition, the results show that, the main contribution for drugs solubility in the aqueous DES solutions is the enthalpy.

Enhanced bioaccesibility of selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide using polyamidoamine dendrimer

The aim of this study was to improve the aqueous solubility of highly hydrophobic but selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide by associating it with polyamidoamine dendrimer. The PAMAM dendrimer restraining ethylenediamine core synthesized by a divergent approach was utilized for encapsulation. The solubility of conjugates was evaluated on the basis of concentration and generation of the dendrimer, pH of the solution, and temperature. The phase solubility diagram confirmed an increase in aqueous solubility of drug with increase in dendrimer concentration with respect to pH in the order 9.0 > 7.0 > 4.0. Moreover, values of thermodynamic parameters such as negative value of ΔHo, positive value of ΔSo and ΔGo reflects an exothermic complexation, presence of number of particles and spontaneity of the complexation. Overall, investigations validate the enhancement in solubility of drug after complexation with polyamidoamine dendrimer which further confirmed promising bioactivity of the drug-dendrimer conjugates.

Formulation of Self-micro Emulsifying Drug Delivery Systems (SMEDDS) of Paclitaxel utilizing factorial design

Background: The antineoplastic drugs possess poor aqueous solubility along with low bioavailability. This limits delivery of antineoplastic drugs through oral route. SMEDDS is a well-accepted means for addressing the lower aqueous solubility and bioavailability issues of a lipophilic drugs. Paclitaxel (PTX) is an antineoplastic drug. PTX is found to be very useful in the treatment of ovarian and breast cancers. PTX have very low aqueous solubility (0.3 µg/ml). 
 Objective: This study aims to formulate SMEDDS incorporating PTX to enhance its aqueous solubility. 
 Methodology: Isopropyl myristate (IM), tween 80 (T80) and transcutol (TC) were used to formulate SMEDDS. IM was considered as oil, T80 as surfactant and TC as co surfactant. 32 factorial design analysis helps in studying the effect of an independent factor on a dependent factor on statistical principles. Independent factors, first – concentrations of oil, second – mixture of surfactant and co-surfactant (Smix), and two dependent factors, first – emulsification time and second – in vitro drug release were chosen. All the nine formulated B1-B9 were subjected to various physicochemical tests. 
 Result and discussion: The globule size was found to be 136.38 – 223.14 nm, zeta potential ranges between -31.54 to -7.58, drug content ranges between 65.34 – 83.56%. Statistical analysis shows that an increasing amount of surfactant decreases emulsification time. This may also decrease the average droplet size of resultant SMEDDS. When the concentration of tween 80 was increased, it was observed that the release of PTX also increased. Rapid and more extent of PTX released from formulated SMEDDS indicates that the aqueous solubility of PTX has increased. B9 formulation releases 99.46% PTX at end of 60 minutes whereas 35.23% of pure PTX powder was solubilized in dissolution medium. 
 Conclusion: This study states that the prepared SMEDDS possess acceptable properties to be considered as immediate release dosage forms. This conclusion was drawn based on in vitro release study.

Ocular delivery of cyclosporine A using dissolvable microneedle contact lens

The penetration of large molecular weight and poorly aqueous soluble drugs within the cornea has been a limiting factor in the treatment of ocular conditions. The objective of the present study was to fabricate rapidly dissolving polymeric microneedle ocular patch (MOP) to effectively deliver cyclosporine A (CsA) within the cornea. Microneedles were prepared using polyvinyl pyrrolidone by micromolding technique with contact lens design features. The model macromolecule, CsA, was loaded in MOP in a bilayered approach, where CsA was entrapped in 25 microneedles. CsA loaded MOP were characterized for physical and mechanical properties, CsA loading, dissolution, corneal insertion, and CsA distribution in excised porcine eye globe. The average height and base diameter of the conical microneedles were 535 ± 15.7 and 287 ± 2.00 μm, respectively. The average amount of CsA loaded in one MOP was found to be 50.3 μg. Microneedles were found to completely dissolve in the cornea within 60 s of application. MOP showed a compression strength of 57.3 ± 13.7 N, and an insertional force of 10.8 ± 0.91 N in the excised porcine cornea. The application of MOP for 5 min significantly (p < 0.05) enhanced the flux (9.04 ± 0.88 μg/cm2/h) and retention (81 ± 5.1 μg/g) of CsA in excised porcine cornea when compared with commercially available Cyclomune® eye drops (flux 2.11 ± 0.56 μg/cm2/h and amount retained 53 ± 1.1 μg/g). The porcine eye globe distribution studies showed a disposition of 45.5, 29.1, 8.3, 5.2, 3.0 and 0.2% of CsA within the cornea, aqueous humor, lens, vitreous humor, sclera and choroid-retinal complex, respectively. Taken together, MOP can be developed for effective ocular delivery of CsA.

Synthesis and characterization of β‐carotene‐loaded albumin nanoparticles by high‐speed homogenizer

Abstractβ‐Carotene (BC) is a strong antioxidant, but its therapeutic application has been limited by its poor aqueous solubility. Protein‐based nanoparticles (NPs) have been used to increase the aqueous solubility of hydrophobic drugs. In this study, bovine serum albumin (BSA) was used to prepare NPs to encapsulate BC using a high‐speed homogenizer. After homogenization, BC‐BSA‐NPs were formed and the encapsulated BC was dissolved in phosphate‐buffered saline at pH 7.4. Various characterization methods, including dynamic light scattering, transmission electron microscopy, and spectrophotometry, indicated that BC‐BSA‐NPs were spherical with an average size of 112 nm and encapsulated BC with high efficiency. BC encapsulated in NPs was stable during the preparation process and was continuously released in PBS at 37 °C for 3 days. The 2,2‐diphenyl‐1‐picrylhydrazyl and ferric reducing antioxidant power assays demonstrated good antioxidant activity of BC‐BSA‐NPs. These results suggest that BSA‐NPs are a promising nanocarrier for the delivery of BC.

Enhanced in vitro therapeutic efficacy of triphenyltin (IV) loaded vitamin E TPGS against breast cancer therapy

Triphenyltin (Ph3SnL (IV) is a synthetic hydrophobic compound functionalized with a diazo and amino group having potentials to use in anticancer chemotherapy, but its hydrophobic property hindrance the therapeutic efficacy for wider use against cancer treatment. Therefore, in our present work we aimed to develop TPGS micelles loaded with Ph3SnL (IV) to enhanced the therapeutic efficacy in breast cancer cells as compare to docetaxel. Solvent casting method was employed to develop TPGS-Ph3SnL1 (IV), TPGS-Ph3SnL5 (IV) and TPGS-DTX micelles to increase the aqueous solubility of hydrophobic drugs. The size of TPGS-Ph3SnL1 (TSD-30-F) and TPGS-Ph3SnL5 (TSD-34-F) micelles were initially evaluated by dynamic light scattering which were found to be below 50 nm. The morphological characteristics of micelles were observed by TEM, SEM and AFM respectively. Further, drug encapsulation and in vitro drug release profiles of micelles were assessed using dialysis bag diffusion technique under sink condition at pH7.4 at 37 °C over 72 h and analysed through UV–visible spectrophotometry. The anticancer efficacy of TSD-30-F, TSD-34-F and DTX-F were tested against two breast cancer cell lines (MCF-7 and MDA-MB-231) and cervical cancer cell line (HeLa) by MTT assay. IC50 values of TSD-30-F and TSD-34-F displayed very high activity towards breast cancer cells as compared to DTX-F, while moderate in case of HeLa cells. Acridine orange/ethidium bromide as well as flow cytometry observation delineates that micelles induced apoptotic mode of cell death after elevating intracellular reactive oxygen level. Higher cellular uptake of micelles in breast cancer cells was evaluated through TPGS-coumarin6 as compared to coumarin6 without TPGS. Therefore, our study suggests that TPGS micelles may increase therapeutics efficacy of Ph3SnL (IV) in breast cancer cells and can be a promising candidate for targeted drug delivery against breast cancer cells.

Effervescent based nano-gas carrier enhanced the bioavailability of poorly aqueous soluble drug: A comprehensive mechanistic understanding

The low aqueous solubility of drug molecules is a considerable hurdle to produce the desired pharmacological effect through any biological route of drug administration. Hence, most of the chemotherapeutic drugs exhibit low bioavailability as well as non-specific toxic effects on the human body. Luteolin (LUT), one of the richest flavonoids, is proven to be a cancer preventive agent for numerous human cancer cell lines. The hydrophobicity of LUT, on the other hand, is a major concern for it's low oral bioavailability. On this account, we have utilized a versatile strategy to engineer a novel effervescent based self-assemble nano-gas drug carrier (NG) for poorly water-soluble compounds, which is hypothesized to be a self-emulsifying agent for drug molecules in the intestinal aqueous environment to form nanoemulsion and eventually escalate the efficacy. The size of the optimized nanoformulation after characterization was found to be 450 ± 100 nm with a negative surface charge (zeta potential value of −27.8 mV). Additionally, SAXS analysis verified the conversion of the carrier into nano-micelles. In vitro studies show NG has a lot of potential for improving LUT's solubility and as a result, LUT can show a significant effect (approximately 2-fold) on pancreatic cancer cell lines at minimal concentration. The permeability enhancement effect of our excipients also showed an additional advantage for the utilization of this concept in the oral formulation development of drug compounds.

Revealing the roles of polymers in supersaturation stabilization from the perspective of crystallization behaviors: A case of nimodipine

Formulating drugs into amorphous solid dispersions (ASDs) represents an attractive means to enhance the aqueous solubility of drugs. Furthermore, water-soluble polymers have proven highly advantageous for stabilizing supersaturated solutions of ASDs. However, the performance and mechanism of various polymers in stabilizing supersaturated drug solutions have not been well-studied. The aim of this study was to investigate the effects of different commercial polymers on the dissolution behaviors and supersaturation stabilization of the ASDs and to further explore the mechanism of polymer mediated supersaturation maintenance by studying the crystallization behaviors of the ASDs. In this study, nimodipine (NMD) was used as a model drug because of its poor water-solubility and fast crystallization rate in aqueous solution, and three polymers polyvinylpyrrolidone (PVP), vinylpyrrolidone-vinyl acetate copolymer (PVP VA), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soluplus) was selected as the drug carriers to form the ASDs with NMD. Solid-state characterizations of the ASDs confirmed the amorphous state of the ASD systems. ASDPVP VA demonstrated superior supersaturation maintenance in dissolution experiments compared to the other two ASD systems. Among the polymers tested, PVP VA most efficiently maintained dissolution of NMD and prevented its crystallization from the supersaturated solution. The ability of PVP VA to most-effectively maintain supersaturation of the drug was manifested by inhibition of crystal nucleation rather than inhibition of crystal growth following nucleation. These results suggest that nucleation inhibition was instrumental in enabling the polymer-mediated supersaturation maintenance, at least with NMD.

Factorial Design Executed Development of Miconazole Nitrate Microemulsion Based Bioadhesive Gel and Its Evaluation

Miconazole nitrate (MN) is a poorly aqueous soluble antifungal drug. The microemulsion (ME) based bioadhesive antifungal gel of MN was designed to improve the antifungal activity by increasing the bioadhesion potential. Based on the solubility results, components of ME were selected viz. rice bran oil: tween 80: propylene glycol and proceeded with pseudo-ternary phase diagram studies. 23 factorial design was employed for the formulation of MEs employing water titration technique. The MEs was examined for further studies and was optimized using DESIGN EXPERT 12 software considering the responses like globule size, zeta potential and in vitro drug release. Tamarind seed polysaccharide (TSP) and carbopol 934 were used as gel bases for the formulation of microemulsion-based bioadhesive gels. The gels were examined for drug content, pH, spreadability, viscosity, bioadhesive strength, ex vivo drug permeation and in vivo skin irritation potential. The antifungal activity against Candida albicans and Cryptococcus neoformans of four formulations (MN-ME, MN- ME based TSP gel, MN- ME based carbopol gel and marketed miconazole gel (2% Miconazole gel) was evaluated using modified agar diffusion method. The results revealed that microemulsion based bioadhesive gel (MBG) of TSP and CP exhibited drug content of about 87.29% and 83.34% and ex vivo skin permeation of 84.21% and 73.94% at the end of 10 h. MBG of TSP showed better antifungal activity and no skin irritation potential in comparison to the carbopol gel. Therefore, MBG of TSP has the ability to enhance the contact time owing to greater bioadhesion thereby providing a better therapeutic activity. Keywords: Miconazole nitrate, Tamarind Gum, Topical delivery, Microemulsion based bioadhesive gel, fungal infection.

Understanding the relationship between solubility and permeability of γ-cyclodextrin-based systems embedded with poorly aqueous soluble benznidazole

When administered orally, the bioavailability of drugs is strongly influenced by their aqueous solubility and permeability. Although solubility-enabling excipients can improve the aqueous solubility of lipophilic drugs, their simultaneous effect on the apparent permeability can be often overlooked. Recently, we demonstrated that the aqueous dissolution of poorly aqueous soluble benznidazole (BNZ) was improved by γ-CD complexation, but the potential impact of γ-CD complexation on the permeability of BNZ remained unexplored. Therefore, the aim of this work was to study the relationship between the aqueous solubility and apparent permeability of BNZ:γ-CD-based formulations, employing both non-cell-based parallel artificial membrane permeability assay (PAMPA) and cell-based (Caco-2 and mucus-producing Caco-2/HT29-MTX co-culture cell model) permeability models. The increase in BNZ aqueous solubility was directly proportional to the γ-CD concentration (from 185 µg mL−1 up to 320 µg mL−1 when 20 mM γ-CD was used in the formulation) and resulted in an increased apparent permeability, though in some cases a decrease was observed. Specifically, in the Caco-2/HT29-MTX cell model an increase in aqueous solubility did not always result in the increase of apparent permeability, with higher γ-CD concentrations leading to a decrease in apparent permeability Papp values down to 3.248 × 10–5 cm s−1 at γ-CD concentration of 30 mM (from 5.164 × 10–5 cm s−1 for 15 mM γ-CD) despite a continuing increase in solubility. Overall, the solubility enhancement of BNZ by γ-CD complexation had different effects on its permeability depending on the permeability model employed, and these effects should be taken into consideration when using solubility-enabling excipients.

Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Marković et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

Cyclodextrin and its derivatives as effective excipients for amorphous ulipristal acetate systems.

Many efforts have been devoted to screening new solid-state forms of poorly soluble drugs in the pharmaceutical industry, thus modulating the drug properties without changing the pharmacological nature. It is a wise strategy to prepare amorphous series with cyclodextrin (CD) and its derivatives as excipients to enhance the aqueous solubility, dissolution, and bioavailability of water-insoluble drugs. In this study, four binary amorphous mixtures of ulipristal acetate (UPA) with CDs (β-CD, γ-CD, dimethyl-β-CD, hydroxypropyl-β-CD) were prepared by the co-milling method and characterized in the solid-state. According to powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC), UPA existed in the noncrystalline form in the four binary amorphous mixtures. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) indicated that UPA interacted with the four CDs, which was also verified by molecular docking. Compared with the crystalline and amorphous UPA, the solubility, dissolution, and stability of the drug in the four amorphous UPA systems were significantly improved, so they were considered potentially advantageous solid forms. Our research shows that CDs can be used as new effective excipients in amorphous systems for active pharmaceutical ingredients (API).

Improved Dissolution of Albendazole from High Drug Loaded Ternary Solid Dispersion: Formulation and Characterization

Bioavailability of a poorly water-soluble drug, e.g., widely used anthelmintic drug Albendazole (ABZ), is very low and thus, to obtain an optimized therapeutic efficacy, the aqueous solubility of such drugs needs to be enhanced. The objective of this study was to develop an effective high drug-loaded solid dispersion (SD) of ABZ with two biocompatible drug carriers, namely Soluplus® and Ludiflash® to improve its physicochemical characteristics. Equilibrium solubility study was performed to choose the optimum polymer ratio among the formulations and it showed up to 50-fold enhanced solubility compared to crystalline ABZ in water. X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) studies of SD-ABZ showed reduced crystallinity of ABZ in the SD. The polymeric carriers, notably Soluplus®, are thought to play a key role in the reduction of crystallinity and molecular polydispersity of ABZ. The dissolution studies in water showed improved dissolution of SD-ABZ compared to crystalline ABZ, with a quick onset of drug release followed by gradual dissolution. However, due to high drug-loading and retention of crystalline ABZ in the sample, the dissolution behavior was not as expected, and may require further studies to optimize the SD-ABZ formulation. Dhaka Univ. J. Pharm. Sci. 20(2): 149-158, 2021 (December)

Progress and Principle of Drug Nanocrystals for Tumor Targeted Delivery.

Drugs are referred to as drug nanocrystals when they exist as nanoscale crystal structures. This kind of nanocarrier has been widely utilized to increase the solubility and absorption for poorly aqueous soluble drugs after oral administration, or prolong the drug circulation when intravenous administration. The systemic cytotoxicity caused by antitumor drugs usually come from the nonspecific drug distribution. To solve the disadvantage of poor targetability, drug nanocrystals for tumor targeted delivery have been developed in recent years. In this review, the targeting mechanisms of various surface modified drug nanocrystals are introduced with the focus on passive targeting, active targeting and stimuli-responsive targeting in details. Function and application of common surface modified materials are also discussed.

Molecular Dynamics Prediction Verified by Experimental Evaluation of the Solubility of Different Drugs in Poly(decalactone) for the Fabrication of Polymeric Nanoemulsions

Nanoemulsions are a rapidly growing drug delivery technology capable of increasing a drug's aqueous solubility and stability. A novel oil‐in‐water nanoemulsion using a polymer, poly(decalactone) (PDL), instead of a conventional oil was recently reported. The amount of drug loading in a polymer‐based formulation is mainly governed by the drug's solubility in the polymer. Thus, herein the power of molecular dynamics simulations (MDS) for the calculation of the Hildebrand solubility parameter to predict PDL–drug miscibility is utilized. The MDS results are subsequently verified by formulating a PDL nanoemulsion with a dispersed droplet size of less than 200 nm by using a block copolymer of PDL (mPEG‐b‐PDL) as a surfactant, with seven different hydrophobic drug molecules. The MDS results are consistent with the experimental findings in terms of increment in the aqueous solubilities of the drugs in PDL nanoemulsion, where celecoxib demonstrated the highest while methotrexate exhibited the lowest solubility increment. Consequently, the reported MDS method can be utilized to predict a drug's solubility/miscibility in PDL to estimate the level of drug loading. The MDS facilitated screening of drugs could consequently emerge as an efficient approach in designing PDL nanoemulsions stabilized by mPEG‐b‐PDL or other similar systems.

Enrichment of aqueous solubility and dissolution profile of mesalamine: In vitro evaluation of solid dispersion

The aim of the present study was to formulate solid dispersion (SD) of Mesalamine to enrich the aqueous solubility and dissolution rate. Mesalamine is used in the management of acute ulcerative colitis and for the prevention of relapse of active ulcerative colitis. In the present study, Solid dispersion of Mesalamine was prepared by Fusion and Solvent evaporation method with different polymers. SD’s were characterized by % practical yield, drug content, Solubility, FT-IR, PXRD (Powder X- ray diffractometry), SEM (Scanning electron microscopy), in vitro dissolution studies and Stability studies. The percent drug release of prepared solid dispersion of Mesalamine by fusion and solid dispersion method (FM47, FM67, SE47 and SE67) in 1:7 ratio was found 81.36±0.41, 86.29±0.64, 82.45±0.57and 87.25±1.14 respectively. The aqueous solubility and percent drug release of solid dispersion of Mesalamine by both methods was significantly increased. The PXRD demonstrated that there was a significant decrease in crystallinity of pure drug present in the solid dispersions, which resulted in an increased aqueous solubility and dissolution rate of Mesalamine.The significant increase in aqueous solubility and dissolution rate of Mesalamine was observed in solid dispersion as the crystallinity of the drug decreased, absence of aggregation and agglomeration, increased wetability and good dispersibility after addition of PEG 4000 and PEG 6000.

Enhancing Etoposide Aqueous Solubility and Anticancer Activity with L-Arginine.

It is hypothesized that L-arginine (ARG) can improve etoposide (VP-16) water solubility while preserving its anticancer activity. Factorial design is used to identify conditions for optimum drug aqueous solubility after freeze-drying. The physicochemical properties of the optimized formulation is further analyzed by X-ray powder diffraction, scanning electron microscopy, proton nuclear magnetic resonance, and fourier transform infrared spectroscopy. Drug stability in formulation is analyzed using mass spectrometry based fragmentation analysis. Liquid chromatography tandem mass spectrometry and cell viability assay on Michigan Cancer Foundation-7 (MCF-7) cell line are performed to assess the drug cellular uptake and the anticancer activity, respectively. At the VP-16: ARG ratio of 4:10 (w/w), the drug apparent solubility increased significantly (∼65-folds) with a 3.5-fold improvement in the drug dissolution rate. The interaction between VP-16 and ARG transforms the drug from crystalline to amorphous solid state. VP-16-ARG complex in lower native drug concentration range (50-300 μM) has lower anticancer activity compared with native VP-16, due to reduced intracellular transport of the more hydrophilic complex as indicated by the cell viability assay and confirmed by cell uptake study. However, at higher drug concentrations (500 μM) the complex's higher anticancer activity is ascribed to the synergistic effect between ARG and VP-16. These data suggest that an optimal ARG concentration can have positive effects with potential benefits for chemotherapy.