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AbstractIntermolecular hydrogen bonding plays a pivotal role in the stability and efficacy of drug-polymer mixtures, which are essential components in modern drug delivery systems. The knowledge of prominent interactions might provide a means to optimize the physiochemical stability of the developed targeted system. Hence, this review explores the fundamental principles of hydrogen bonding in drug-polymer interactions which can significantly influence the solubility, stability and release profiles of pharmaceutical formulations. The review provides an in-depth examination of the types of functional groups that participate in hydrogen bonding, the characterization techniques employed to study these interactions and the implications of hydrogen bonding on drug delivery. Case studies of successful drug-polymer systems stabilized by hydrogen bonding are presented, highlighting the practical applications and challenges associated with these formulations. Furthermore, the review discusses the future perspectives in this field, including the design of novel polymers and the integration of computational modeling to predict hydrogen bonding behavior. By understanding and leveraging hydrogen bonding, researchers can optimize drug delivery systems, ensuring enhanced bioavailability, controlled release and improved patient outcomes. This review aims to serve as a comprehensive resource for pharmaceutical scientists and formulators, offering insights into the strategic use of hydrogen bonding to develop more effective and stable drug delivery systems. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding. [ABSTRACT FROM AUTHOR]

Transglycosylation has been used to modify the physicochemical properties of original compounds. As a result, transglycosylated compounds can form molecular aggregates in size ranges of a few nanometers in an aqueous medium when their concentrations exceed a specific level. Incorporating these hydrophobic compounds has been observed to enhance the solubility of hydrophobic compounds into aggregate structures. Thus, this review introduces four transglycosylated compounds as food additives that can enhance the solubility and oral absorption of hydrophobic compounds. Here, transglycosylated hesperidin, transglycosylated rutin, transglycosylated naringin, and transglycosylated stevia are the focus as representative substances. Significantly, we observed that amorphous formations containing hydrophobic compounds with transglycosylated compounds improved solubility and oral absorption compared to untreated hydrophobic compounds. Moreover, combining transglycosylated compounds with hydrophilic polymers or surfactants enhanced the solubilizing effects on hydrophobic compounds. Furthermore, the enhanced solubility of hydrophobic compounds improved their oral absorption. Transglycosylated compounds also influenced nanoparticle preparation of hydrophobic compounds as a dispersant. This study demonstrated the benefits of transglycosylated compounds in developing supplements and nutraceuticals of hydrophobic compounds with poor aqueous solubility. [ABSTRACT FROM AUTHOR]

The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL. [ABSTRACT FROM AUTHOR]

This study aims to compare the effect of different drying techniques (oven-, spray-, and freeze drying) on xanthone, a poorly aqueous-soluble bioactive compound, encapsulated by coacervation using gelatin and gum Arabic. Free-flowing spherical shape powders were produced except for freeze drying that resulted in a stratified cell-like structure. Fourier transform infrared spectroscopy confirmed no interaction between xanthone and wall material. Among the drying techniques, spray dried resulted in the lowest yield and encapsulation efficiency (EE) but the highest improvement (ninefold) in xanthone aqueous solubility from 2.6 µg/mL to 22.32 ± 5.99 µg/mL. Freeze drying resulted in the highest encapsulation yield (75.4%) and EE (68.2%). Besides the solubilizing effect of wall material, the drying technique demonstrates a significant effect (p < 0.05) on xanthone's aqueous solubility. In summary, this study provides insights into the influence of drying techniques on the physicochemical properties of xanthone coacervates, which has potential usage in food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The aim of this study is, preparing various dendrimeric formulations of oxaliplatin and investigating their properties. First of all, the solubility enhancement capabilities of polyamidoamine (PAMAM) G3.5 and PAMAM G4.5 dendrimers were investigated. The results showed that oxaliplatin solubility mostly increasing linearly with dendrimer concentration. Additionally, the increase was more notable in PAMAM G4.5 dendrimers. Then, drug–dendrimer complexes were prepared in different mediums, since the medium used can affect the amount of drug-loaded to dendrimers. Prepared complexes were examined for loading capacity and loading efficiency. It was found that PAMAM G4.5 dendrimers can complex with 2- to 5-fold more oxaliplatin than PAMAM G3.5. Finally, oxaliplatin was modified to a platinum (IV) compound to prepare chemical drug–dendrimer conjugates. Ester bonds were established by Steglich esterification through the hydroxyl group of modified oxaliplatin and the carboxyl groups of the dendrimers. The formulations were characterized by UV, IR, NMR spectroscopy, and dynamic light scattering techniques. PAMAM G3.5 conjugate was further evaluated for the cytotoxicity test. The IC50 value of PAMAM G3.5 conjugate was found as 0.72 µM. For unmodified oxaliplatin, this value was 14.03 µM. As a result, a dendrimer-based drug delivery system that has been found promising for further improvement has been developed successfully. [ABSTRACT FROM AUTHOR]

Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an antiparasitic, antibacterial and antiviral agent. NTZ is a highly low aqueous soluble drug which possesses solubility of 0.00755 mg/mL and typically low bioavailability of 1%. Low aqueous solubility is usually regarded as prime prerequisites for enhanced absorption and bioavailability. The purpose of this study is to improve in vitro dissolution of the poorly soluble drug NTZ through amorphous solid dispersion technology. Three solid dispersions of NTZ were successfully prepared by hot-melt technique. It was further evaluated for drug content, DSC, XRD, SEM, TEM, FT-IR, in-vitro drug release study, in vitro MTT safety on HEK-293 and A-549 and stability study. The results of XRD showed after the formation of solid dispersions. The number of crystalline peaks has disappeared and confirmed the amorphous form of the drug. An in vitro release study showed that NTZ effectively released from solid dispersion into a simulated gastric releasing medium (pH 1.2). Further, the cytotoxicity study gave an indication of safe for human. Also, stability studies depicted no evident difference in the physical state of solid dispersion after six months. Hence, it can be concluded that the newly developed formulation was found to be safe and stable with enhanced solubility profile. [ABSTRACT FROM AUTHOR]

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop resveratrol nanocrystals to solve low water solubility issues of resveratrol and adsorb them to the polycaprolactone nanofibers. Nanocrystals were prepared by microfluidization. Particle size, polydispersity index and zeta potential values were evaluated as dependent variables. Polycaprolactone (PCL) nanofibers were prepared via electrospinning method and the flow rate, electrical voltage and tip-to-collector distance were set to 3 mL/h, 13 kV and 15 cm, respectively. Optimum resveratrol nanocrystals were lyophilized and re-suspended in water and physically adsorbed to PCL nanofibers with two different concentrations (0.2 and 1 mg/cm2). Bioadhesion, wettability, solubility, drug loading and antimicrobial activity against Propionibacterium acnes studies were carried out. Final nanocrystals showed 800 nm of particle size, 0.4 of polydispersity index, and −8 mV of zeta potential. Nanocrystals successfully adsorbed to PCL nanofibers proven on SEM images with adsorption efficiencies >70%. Adsorption of resveratrol nanocrystals decreased the contact angle of PCL from 128° to 50°. The solubility of resveratrol nanocrystals enhanced ∼5-fold in comparison with coarse powder. Effective antimicrobial activity against P. acnes was observed. It is concluded that nanocrystal loading on nanofibers brings advantage into preparing easy to use dermal patches for acne treatment or skin disorders. [ABSTRACT FROM AUTHOR]

Present work demonstrated the influence of novel amphiphilic carrier Soluplus® on the solubility and oral bioavailability of Morin hydrate (MOR). Spray-dried solid dispersions (SSD) were developed using the design of experiment (DoE). Saturation solubility study of the optimized formulation SSD F(7) showed many fold increment in the solubility with acceptable aqueous stability. In vitro drug diffusion kinetics suggested Weibull model to be the best fit. In vitro cytotoxicity assay revealed a significant increase in the anticancer potential compared to innate MOR. Furthermore, SSD F(7) showed 2.27-fold enhancement in the relative bioavailability as compared to MOR. BCS: biopharmaceutical classification system; MOR: Morin hydrate; SD: solid dispersion; SSD: spray dried solid dispersion; PM: physical mixture; CCD: central composite design; PSD: particle size distribution; PDI: polydispersity index; SEM: scanning electron microscopy; XRD: X-ray diffraction; DSC: differential scanning calorimetry; TGA: thermal gravimetric analysis; DTA: differential thermal analysis; DTG: derivative thermogravimetry; Tg: glass transition temperature; API: active pharmaceutical ingredient; P-gp: permeability glycoprotein; SRB: sulforhodamine B; ADR: adriamycin; DoE: design of experiment [ABSTRACT FROM AUTHOR]

L-NG-nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration. This work, for the first time, details a systematic study on the determination of equilibriumKaconstants and the rate law of LNNA degradation. The fourKavalues of LNNA were determined to be 1.03, 1.10 × 10−2, 2.51 × 10−10, and 1.33 × 10−13 M. From the kinetic and equilibrium studies, we have shown that the deprotonated form of LNNA is the main form of LNNA that undergoes degradation in aqueous media at room temperature. The rate law of LNNA degradation was found to be first order with respect to OH−concentration and first order with respect to LNNA−concentration. The rate constant at 25 °C and 1 atm was determined to be 0.04453 M−1min−1. A base catalyzed mechanism of LNNA degradation was proposed based on the kinetic study. The mechanism was found to be very useful in explaining the discrepancies and changes of the rate law at different pH values. It is thus recommended that LNNA should be formulated as a concentrated solution in acidic conditions for maximum chemical stability during storage and be diluted with a basic solution to near physiological pH just before administration. [ABSTRACT FROM AUTHOR]

Poly(2-hydroxyethylmethacrylate-graft-ibuprofen) (IpGH) of different ibuprofen (Ibu) contents was prepared by grafting of Ibu groups on poly(2-hydroxyethyl methacrylate) (PHEMA) in an esterification reaction route. The resulted copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry, thermal gravimetric analysis, X-ray diffraction, and scanning electron microscope analysis. The cytotoxicity test and the free radical scavenging ability of this material were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) and 1,1-diphenyl-2-picryl-hydrazyl assay methods, respectively. Thein vitrorelease study of Ibu through a retro-esterification reaction of IpHG material during 3 days reveals that the release dynamic depends on the initial Ibu grafted, pH media, and the swelling degree of PHEMA. It was also revealed that the water solubility of Ibu easily reached a maximum of 0.216 mg mL−1. The diffusion of Ibu through the polymer matrix obeys the Fickian model. The estimated distribution of the cumulative drug released in different simulated digestive organs reveals that the IpHG7 containing 6.69 mol% of Ibu content showed the best performance. [ABSTRACT FROM AUTHOR]

The aim of this study was to enhance aqueous solubility of xanthone with natural polymers using oil-in-water emulsion and complex coacervation as the microencapsulation techniques. There was no interaction between xanthone and the wall material; and xanthone crystallinity was decreased as observed via fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and x-ray powder diffraction (XRD) after microencapsulation. Oil-in-water emulsion and coacervation increased xanthone solubility by 37-fold and 1.6-fold, respectively. However, O/W emulsion method required a high ratio of oil to xanthone. The solubilizing effect of oil and wall material, particle size reduction, and decreased crystallinity were responsible for enhancing the aqueous solubility of xanthone. [ABSTRACT FROM AUTHOR]

Poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) was synthesized by free radical polymerization of 2-hydroxyethylmethacrylate with 2-folatethylmethacrylate and folic acid/poly(2-hydroxyethylmethacrylate) solid solutions was prepared by mixing folic acid with poly(2-hydroxyethylmethacrylate) using the solution casting method. The structure and the homogeneity distribution of folic acid in the polymer matrix are characterized by different methods. The diffusion behaviors of water and folic acid through poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) and poly(2-hydroxyethylmethacrylate) matrixes were found obey to the Fick models. The in vitro cytotoxicity assessed by microculture tetrazolium test assay and the antioxidant activity of poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) systems determined by 1,1-diphenyl-2-picryl-hydrazyl method revealed no significant toxicity of these systems and has excellent free radical scavenger property which can be as safe candidate in drug-carrier system. The solubility enhancement of folic acid in different pH media is also investigated and the results obtained reveal a maximum of 399–400 mg L−1. The release dynamic of folic acid from the poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) containing 5 mol% of folic acid and that from folic acid/poly(2-hydroxyethylmethacrylate) system containing 10 mol% of folic acid have the best intestine/stomach ratio. [ABSTRACT FROM PUBLISHER]

This study focused on the solubility enhancement and thein vivoantidotal efficacy testing of a new potential cyanide (CN) countermeasure, dimethyl trisulfide (DMTS). Various FDA approved cyclodextrins (HPβCD, RMβCD, HPγCD), cosolvents (ethanol, polyethylene glycols, propylene glycol), surfactants (cremophor EL, cremophor RH 40, sodium cholate, sodium deoxycholate, polysorbate 80) and their combinations were applied. Based on the solubility enhancing potential of the tested systems, polysorbate 80 was chosen for furtherin vivoefficacy studies. A composition comprising 15% polysorbate 80 and 50 mg/ml DMTS with the applied DMTS dose of 100 mg/kg provided a therapeutic antidotal protection of 3.4 × LD50. For comparison, the present therapy of sodium thiosulfate (TS) with the dose of 100 mg/kg provided only 1.1 × LD50protection, and at the dose of 200 mg/kg, the LD50was enhanced by 1.3 times. No difference in the therapeutic protection by DMTS was detected when the concentration of polysorbate 80 was increased to 20% (3.2 × LD50protection). These data demonstrate the potential importance of DMTS as a CN countermeasure, and the formulation comprising polysorbate 80 provides the base of an injectable intramuscular dosage form that can later serve as a CN antidotal kit suitable for mass scenario. [ABSTRACT FROM AUTHOR]

Poor water solubility of hydrophobic drugs is one of the major problems in pharmaceutical sciences. Herein, in order to address the poor solubility of crocetin, the 30% of primary amines of PAMAM G4 and PPI G4 were alkylated and evaluated as drug delivery vectors. According to the results, this modification could improve the drug delivery efficiency in term of drug solubility, release pattern and cytotoxicity; however, the encapsulation yield was decreased. Accordingly, it can be concluded that the designed alkylated dendrimers are able to improve the drug delivery efficiency, may be through improving the solubility and cellular uptake of crocetin. [ABSTRACT FROM AUTHOR]

Background:Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. Method:Five different ILs were prepared—three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. Results:Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. Conclusions:Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations. [ABSTRACT FROM PUBLISHER]

Asenapine maleate (AM) is used in the treatment of schizophrenia. Its oral and sublingual bioavailability is <2% and 35%, respectively, due to first pass metabolism and poor solubility. To avoid first pass metabolism and to enhance solubility at all nasal pH conditions, thermo-responsivein situnasal gel containing asenapine maleate-hydroxyl propyl β cyclodextrin inclusion complex (AM-HPβCD) was prepared in the present study. Inclusion complex (1:1 molar ratio) was characterized using UV spectroscopy, FITR and XRD techniques. Selected formulation (F8b) contained a thermo-sensitive polymer poloxamer 407 which formed gel at 23%w/v concentration and a mucoadhesive polymer PVP K 30 (0.3%w/v) in temperature range of 29–34 °c. It was analyzed for pH, clarity, gelation temperature, mucoadhesive strength, gel strength and rheological parameters using Anton paar compact rheometer. This formulation was subjected toin vitrodrug diffusion study using the Franz diffusion cell. Maximum % drug diffusion was obtained at the end of 120 min (99.1 ± 0.44%w/v). Dissolution in simulated nasal fluid was 92.33 ± 0.15%w/v at the end of 120 min. Locomotor activity was improved with nasal gel containing AM-HPβCD as compared to AM and AM-HPβCD oral solution in rats.Cmaxfor nasal gel was found to be more (9 ng/ml) as compared to AM-HPβCD (5.5 ng/mL) and oral standard solution (2 ng/ml).Tmaxwas found to be 1.5 h. AUC and thus bioavailability in rats by nasal route was increased by 2.5 fold. [ABSTRACT FROM AUTHOR]

A series of poly (2-hydroxyethylmethacrylate-graft-folic acid) (FAHEMA) systems are synthesized by grafting of folic acid (FA) into poly (2–hydroxyethylmethacrylate) via an esterification reaction. The structure of these copolymers is confirmed by NMR and CHN analyses. The thermal behavior of these materials is characterized by DSC and TGA analyses. The surface morphology of FAHEMA films before and after the release process is examined by the SEM method. The cumulative FA released in different pH media from FAHEMA materials occurred via a retro-esterification reaction at body temperature during 72 h in which the influence of the swelling degree of PHEMA, the FA content and pH media on the dynamic release is widely investigated. The results obtained revealed that the solubility of FA in water deduced from the release process is widely improved compared with literature reports. It is also revealed that the diffusion of water in different pH media through the PHEMA matrix and that of FA through FAHEMA materials perfectly obeyed the Fickian models. It was deduced from the kinetic study that the release performance is obtained with the copolymers containing initially 10 and 20 wt% of FA contents. [ABSTRACT FROM PUBLISHER]

Clotrimazole (CT) is a poorly soluble antifungal drug that is most commonly employed as a topical treatment in the management of vaginal candidiasis. The present work focuses on a formulation approach to enhance the solubility of CT using cyclodextrin (CD) complexation. A CT–CD complex was prepared by a co-precipitation method. Various characterization techniques such as differential scanning calorimetry, infrared (IR) and X-ray spectroscopy, scanning electron microscopy and nuclear magnetic resonance (NMR) spectroscopy were performed to evaluate the complex formation and to understand the interactions between CT and CD. Computational molecular modeling was performed using the Schrödinger suite and Gaussian 09 program to understand structural conformations of the complex. The phase solubility curve followed anAL-type curve, indicating formation of a 1:1 complex. Molecular docking studies supported the data obtained through NMR and IR studies. Enthalpy changes confirmed that complexation was an exothermic and enthalpically favorable phenomenon. The CT–CD complexes were formulated in a gel and evaluated for release and antifungal activity. Thein vitrorelease studies performed using gels demonstrated a sustained release of CT from the CT–CD complex with the complex exhibiting improved release relative to the un-complexed CT. Complexed CT–CD exhibited better fungistatic activity toward differentCandidaspecies than un-complexed CT. [ABSTRACT FROM PUBLISHER]

Efavirenz is a non-nucleoside reverse transcriptase inhibitor, and is classified as BCS Class II API. Its erratic oral absorption and poor bioavailability make it a potential candidate for being formulated as a nanosuspension. The objective of this study was to formulate efavirenz nanosuspensions employing the antisolvent precipitation-ultrasonication method, and to enhance its solubility by reducing particle size to the nanometer range. The effects of different process parameters were studied and optimized with respect to particle size and poly dispersity index (PDI). The optimized formulation was also subjected to lyophilization, to further increase the solubility and stability, and the technology is potentially suited to a range of poorly water-soluble compounds. [ABSTRACT FROM AUTHOR]

Objective of present study was to develop formulation which improves solubility of furosemide and stability of spray dried solid dispersion. Various processing parameters were optimized by applying DoE. In first step, screening of poly(meth)acrylates were carried out using solvent casting methods to select appropriate polymer. In second step, solid dispersion was prepared using optimized poly(meth)acrylate via spray drying process and trials were conducted as per DoE. Characterization of spray dried microparticles was carried out using SEM, DSC, XRD, in-vitro dissolution, and stability study. EUDRAGIT® E PO was screened as a suitable polymeric carrier in solvent casting method. In-vitro dissolution showed 100% releases within 20 min for spray dried powder as compared to 9% release for pure drug after 60 min in 0.1 N HCl. SEM analysis revealed conversion of crystalline shape to spherical shape. DSC and XRD confirmed that crystalline form was converted into amorphous form which was stable even after 3 months of storage. Outcome of DoE revealed that, feed rate has significant effect on %LOD while solid content has major effect on the process yield. So, present work indicates that EUDRAGIT® E PO formed a stable spray dried solid dispersion and it has ability to enhance dissolution of furosemide. [ABSTRACT FROM AUTHOR]

The objective of this paper is to introduce some strategic guidance to a rational formulation strategy of new molecules as oral dosage forms, based on a sound scientific understanding of factors determining the oral bioavailability. The critical implication of permeability and solubility is discussed along with the efficient dose of the drug. The concept of dose-solubility number is introduced as a tool for chemists to assess the develop-ability of different molecules very early during discovery stage. Based on this understanding, a rational formulation strategy for preclinical and early clinical phases is provided. The technical considerations and limitations of different formulation technologies are discussed and illustrated via concrete examples. This approach has the advantage of streamlining the formulation process in order to avoid delaying the development of new drugs due to formulation related issues. [ABSTRACT FROM PUBLISHER]

A series of copolymers were prepared by grafting of simvastatin (SIM) to poly(methacrylic acid) (PMAA) in an esterification reaction with removal water. The resulted copolymers were then crossinlked by using ethylene glycol to form PMAA-graft-SIM hydrogels (SIMA). The FTIR and NMR spectroscopy analyses revealed that the intetramolecular six membered cyclic anhydride units were formed in the PMAA-graft-SIM main chains. The influences of pH media and SIM composition on the retroesterification reaction of SIMA to release SIM were widely investigated. It was observed that the diffusion coefficient of SIM in polymer matrix followed a Fickian model. The kinetic study of SIM released from SIMA films revealed that, at pH 7 (intestines media), SIMA13 showed the higher performance, because this material was capable to release a higher SIM amount (59.00 ± 1.06 wt%) uniformly with a rate of 1.11 ± 0.02 wt%/h during 53 h of the release process. However, this material was capable to release uniformly only a maximum of 9.99 ± 0.09 wt% of SIM at pH 1 (stomach media) during the first 3 h. [ABSTRACT FROM AUTHOR]

In recent years, nanosponges (NS) have gained tremendous impetus in drug delivery through nanotechnology. Nanosponges are capable of providing solutions for several formulation related problems. Through this review, scientists working in the field of nanotechnology can have an insight into the techniques of preparation, characterization and applications of NS. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability. They can be crafted for targeting drugs to specific sites, prevent drug and protein degradation and prolong drug release in a controlled manner. This review attempts to elaborate different schemes of synthesis of NS and their characterization. Factors affecting drug loading and release have been enumerated. Due to their advantages, NS have not only been explored for their pharmaceutical applications but also have large popularity in allied sciences, especially in water purification. [ABSTRACT FROM AUTHOR]

Background: Quercetin (QC) is a poorly water-soluble and degradation-prone bioflavonoid. Aim: This study aimed to investigate the formation of a chemically stable and readily water-soluble solid complex of QC with hydroxypropyl-β-cyclodextrin (HP-β-CD). Method: A solid HP-β-CD/QC complex was prepared by spray drying and characterized by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, scanning electron microscopy, laser-diffraction particle sizing, powder X-ray diffraction, thermal analysis, Brunauer–Emmett–Teller nitrogen adsorption, and dissolution testing. Results: The complex displayed excellent thermal stability during spray drying, a broad diffuse X-ray diffraction pattern, and a single glass transition temperature ( Tg) characteristic of amorphous HP-β-CD. Dissolution testing of the complex in simulated gastric fluid revealed an approximately eightfold increase in the rate and extent of dissolution of QC compared with its molar equivalent physical mixture of QC and blank spray-dried HP β-CD, although the surface area of QC in the mixture was about seven times that of the complex. Conclusions: All these observations can be explained by specific interaction between QC and HP-β-CD in the amorphous solid state, possibly in the form of an inclusion complex. [ABSTRACT FROM AUTHOR]

Co-solvent solubilization approach has been used to enhance the solubility of seven antidiabetic drugs: gliclazide, glyburide, glipizide, glimepiride, repaglinide, pioglitazone, and roziglitazone. Solubility in water, phosphate buffer (pH 7.4), six co-solvent solutions prepared in water as well as phosphate buffer (pH 7.4) and pH-solubility profile of various drugs have been determined at 25°C. Aqueous solubility of various drugs was found to be less than 0.04 mg/mL. Solubility of gliclazide, glipizide and repaglinide increased by 3-6 times by using phosphate buffer (pH 7.4) as solvent. Solubility enhancement by pH modification was not sufficient. Significant enhancement in solubility could be achieved by the use of co-solvents. The combined effect of co-solvent and buffer was synergistic and enormous increase in solubility of sulfonylureas and repaglinide could be achieved. In the case of glitazones, however, co-solvent alone caused significant enhancement; the presence of buffer had negative effect on the solubilization potential of the co-solvents. Up to 763, 316, 153, 524, 297, 792 and 513 times increase in solubility could be achieved in the case of gliclazide, glyburide, glimepiride, glipizide, repaglinide, pioglitazone and rosiglitazone, respectively. [ABSTRACT FROM AUTHOR]

This work includes investigation on solubility enhancement of indomethacin (IND) in the presence of poly(amidoamine) (PAMAM) dendrimers and passive targeting of the PAMAM/IND complex so formed to the inflamed regions in an animal model. The complex formation was confirmed by infrared and 1 H nuclear magnetic resonance spectroscopy methods. Solubility of IND in aqueous G4-PAMAM followed Higuchi's A N curve depending on pH of the solubilizing medium. The solubility was decreased upon addition of dendrimer to the IND saturated solution at various pH, indicating aggregation behavior of the PAMAM/IND complex and conforming to the Higuchi's A N solubility profile. The in vitro release of IND from the PAMAM/IND complex through a cellophane membrane, from a Franz diffusion cell, showed 79±3.2% drug release in 24 h. The drug release was further retarded in the presence of human serum albumin (HSA) suggesting the significance of complex HSA binding in altering in vivo behavior of the complex. Intravenous administration of the PAMAM/IND complex formulation in rats showed a two-compartment pharmacokinetic profile. Enhanced effective IND concentrations in the inflamed regions were obtained for the prolonged time period with the PAMAM/IND complex compared to the free drug in arthritic rats indicating preferred accumulation of IND to the inflamed region. The targeting efficiency of PAMAM/IND complex was 2.29 times higher compared to free drug. In contrast to the previous investigations, two interesting findings reported here are: (a) solubility behavior of IND in G4-PAMAM dendrimer deviates from linearity with increasing concentrations of dendrimer at acidic to neutral pH values and (b) inspite of lymphatic drainage, retention of PAMAM/IND complexes occurs at the inflammatory site. [ABSTRACT FROM AUTHOR]

1,5-Diazaanthraquinones (DAQs) are promising anticancer drugs, however, their clinical potential is limited due to poor solubility. Conjugation of anticancer agents to hydrophilic water-soluble polymers can overcome this problem and has already been used to generate conjugates with demonstrated clinical benefit. Here a library of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates containing a novel amino-functionalised 1,5-diazaanthraquinone derivative (amino-DAQ) have been synthesised. The conjugates were fully characterised by UV, HPLC, SEC, FT-Raman and NMR spectroscopy. Conjugation to HPMA copolymers improved amino-DAQ aqueous solubility (>7-fold). The HPMA copolymer-amino-DAQ conjugates were slightly less haemolytic than the parent compound (2% Hb released in 1 h for conjugate HPMA copolymer-GFLG (5 mol%)-amino-DAQ conjugate compared to 13% obtained with amino-DAQ). When conjugates were incubated with isolated rat liver lysosomal enzymes (Tritosomes) the rate of amino-DAQ release was influenced by both drug loading and the composition of the peptidyl side chain used to link the drug to the carrier. The higher the drug loading the lower the rate of drug release. Whereas the GG linker did not release amino-DAQ, up to 26% of the amino-DAQ was released from a GFLG linker over 24 h. The in vitro cytotoxicity of these conjugates was evaluated against two different cell lines, B16F10 murine melanoma and MCF-7 human breast cancer cells. HPMA copolymer-amino-DAQ conjugates, which are internalised by cells by the endocytic pathway, showed much lower in vitro cytotoxicity (IC 50 for HPMA copolymer-GFLG (5 mol%)-amino-DAQ conjugate > 397 μM drug-equiv.) than the free drug (the IC 50 for amino-DAQ was 12.6 and 2.8 μM against the B16F10 murine melanoma and the MCF-7 breast cancer cell line, respectively). Nonetheless, the observed lysosomal activation of the HPMA copolymer-GFLG-amino-DAQ conjugates, suggests that evaluation of the antitumour potential in vivo is warranted. [ABSTRACT FROM AUTHOR]