Niclosamide-loaded nanoparticles disrupt Candida biofilms and protect mice from mucosal candidiasis.

Candida albicans biofilms are a complex multilayer community of cells that are resistant to almost all classes of antifungal drugs. The bottommost layers of biofilms experience nutrient limitation where C. albicans cells are required to respire. We previously reported that a protein Ndu1 is essential for Candida mitochondrial respiration; loss of NDU1 causes inability of C. albicans to grow on alternative carbon sources and triggers early biofilm detachment. Here, we screened a repurposed library of FDA-approved small molecule inhibitors to identify those that prevent NDU1-associated functions. We identified an antihelminthic drug, Niclosamide (NCL), which not only prevented growth on acetate, C. albicans hyphenation and early biofilm growth, but also completely disengaged fully grown biofilms of drug-resistant C. albicans and Candida auris from their growth surface. To overcome the suboptimal solubility and permeability of NCL that is well known to affect its in vivo efficacy, we developed NCL-encapsulated Eudragit EPO (an FDA-approved polymer) nanoparticles (NCL-EPO-NPs) with high niclosamide loading, which also provided long-term stability. The developed NCL-EPO-NPs completely penetrated mature biofilms and attained anti-biofilm activity at low microgram concentrations. NCL-EPO-NPs induced ROS activity in C. albicans and drastically reduced oxygen consumption rate in the fungus, similar to that seen in an NDU1 mutant. NCL-EPO-NPs also significantly abrogated mucocutaneous candidiasis by fluconazole-resistant strains of C. albicans, in mice models of oropharyngeal and vulvovaginal candidiasis. To our knowledge, this is the first study that targets biofilm detachment as a target to get rid of drug-resistant Candida biofilms and uses NPs of an FDA-approved nontoxic drug to improve biofilm penetrability and microbial killing.

Challenges and advancements in membrane distillation crystallization for industrial applications.

Membrane distillation crystallization (MDC) is an emerging hybrid thermal membrane technology that synergizes membrane distillation (MD) and crystallization, which can achieve both freshwater and minerals recovery from high concentrated solutions. Due to the outstanding hydrophobic nature of the membranes, MDC has been widely used in numerous fields such as seawater desalination, valuable minerals recovery, industrial wastewater treatment and pharmaceutical applications, where the separation of dissolved solids is required. Despite the fact that MDC has shown great promise in producing both high-purity crystals and freshwater, most studies on MDC remain limited to laboratory scale, and industrializing MDC processes is currently impractical. This paper summarizes the current state of MDC research, focusing on the mechanisms of MDC, the controls for membrane distillation (MD), and the controls for crystallization. Additionally, this paper categorizes the obstacles hindering the industrialization of MDC into various aspects, including energy consumption, membrane wetting, flux reduction, crystal yield and purity, and crystallizer design. Furthermore, this study also indicates the direction for future development of the industrialization of MDC.

Coumarinolignans with Reactive Oxygen Species (ROS) and NF-κB Inhibitory Activities from the Roots of Waltheria indica.

Seven new coumarinolignans, walthindicins A-F (1a, 1b, 2-5, 7), along with five known analogs (6, 8-11), were isolated from the roots of Waltheria indica. The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 µg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293).

In vitro efficacy of anthelmintics on Angiostrongylus cantonensis L3 larvae.

Angiostrongylus cantonensis is the leading cause of eosinophilic meningitis worldwide, with life-threatening complications if not managed correctly. Previous in vitro studies have utilized change in motility patterns of adult female worms to assess the efficacy of anthelmintics qualitatively. However, it is the third stage larvae (L3) that are infectious to humans. With differential staining using propidium iodide penetration as the indicator of death, we can distinguish between dead and live larvae. This assay has enabled us to quantify the in vitro efficacy of nine clinically established anthelmintics on A. cantonensis L3. All drugs were tested at a 1 mm concentration. Piperazine and niclosamide were ineffective in inducing larval death; however, albendazole sulfoxide, pyrantel pamoate, diethylcarbamazine, levamisole and praziquantel were effective as compared to unexposed controls (P < 0.05). Ivermectin and moxidectin did not induce significant levels of mortality, but they considerably reduced larval motility almost immediately. This study indicates the need for further in vivo studies to determine the optimal dose and time frame for post-infection treatment with anthelmintics that demonstrated efficacy.

Hypo-osmolar Formulation of Tenofovir (TFV) Enema Promotes Uptake and Metabolism of TFV in Tissues, Leading to Prevention of SHIV/SIV Infection.

Oral preexposure prophylaxis (PrEP) has been approved for prophylaxis of HIV-1 transmission but is associated with high costs and issues of adherence. Protection from anal transmission of HIV using topical microbicides and methods congruent with sexual behavior offers the promise of improved adherence. We compared the pharmacokinetics (PK) and ex vivo efficacy of iso-osmolar (IOsm) and hypo-osmolar (HOsm) rectal enema formulations of tenofovir (TFV) in rhesus macaques. Single-dose PK of IOsm or HOsm high-dose (5.28 mg/ml) and low-dose (1.76 mg/ml) formulations of TFV enemas were evaluated for systemic uptake in blood, colorectal biopsy specimens, and rectal CD4+ T cells. Markedly higher TFV concentrations were observed in plasma and tissues after administration of the HOsm high-dose formulation than with all other formulations tested. TFV and TFV diphosphate (TFV-DP) concentrations in tissue correlated for the HOsm high-dose formulation, demonstrating rapid uptake and transformation of TFV to TFV-DP in tissues. TFV-DP amounts in tissues collected at 1 and 24 h were 7 times and 5 times higher, respectively (P < 0.01), than the ones collected in tissues with the IOsm formulation. The HOsm high-dose formulation prevented infection in ex vivo challenges of rectal tissues collected at 1, 24, and 72 h after the intrarectal dosing, whereas the same TFV dose formulated as an IOsm enema was less effective.

Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission.

Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital and coitus-independent HIV prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered in a thermosensitive gel, which becomes solid at body temperature. PLGA nanoparticles with encapsulated rilpivirine coated the reproductive tract and offered significant protection to BLT humanized mice from a vaginal high-dose HIV-1 challenge. A different nanosuspension of crystalline rilpivirine (RPV LA), administered intramuscularly, protected BLT mice from a single vaginal high-dose HIV-1 challenge one week after drug administration. Using transmitted/founder viruses, which were previously shown to establish de novo infection in humans, we demonstrated that RPV LA offers significant protection from two consecutive high-dose HIV-1 challenges one and four weeks after drug administration. In this experiment, we also showed that, in certain cases, even in the presence of drug, HIV infection could occur without overt or detectable systemic replication until levels of drug were reduced. We also showed that infection in the presence of drug can result in acquisition of multiple viruses after subsequent exposures. These observations have important implications for the implementation of long-acting antiretroviral formulations for HIV prevention. They provide first evidence that occult infections can occur, despite the presence of sustained levels of antiretroviral drugs. Together, our results demonstrate that topically- or systemically administered rilpivirine offers significant coitus-dependent or coitus-independent protection from HIV infection.

Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal Transmission in a Humanized Mouse Model.

Preexposure prophylaxis (PrEP) with 1% tenofovir (TFV) vaginal gel has failed in clinical trials. To improve TFV efficacy in vaginal gel, we formulated tenofovir disoproxil fumarate nanoparticles in a thermosensitive (TMS) gel (TDF-NP-TMS gel). TDF-NPs were fabricated using poly(lactic-co-glycolic acid) (PLGA) polymer and an ion-pairing agent by oil-in-water emulsification. The efficacy of TDF-NP-TMS gel was tested in humanized bone marrow-liver-thymus (hu-BLT) mice. Hu-BLT mice in the treatment group (Rx; n = 15) were administered TDF-NP-TMS gel intravaginally, having TDF at 0.1%, 0.5%, and 1% (wt/vol) concentrations, whereas the control (Ctr; n = 8) group received a blank TMS gel. All Rx mice (0.1% [n = 4], 0.5% [n = 6], and 1% [n = 5]) were vaginally challenged with two transmitted/founder (T/F) HIV-1 strains (2.5 × 10(5) 50% tissue culture infectious doses). Rx mice were challenged at 4 h (0.1%), 24 h (0.5%), and 7 days (1%) posttreatment (p.t.) and Ctr mice were challenged at 4 h p.t. Blood was drawn weekly for 4 weeks postinoculation (p.i.) for plasma viral load (pVL) using reverse transcription-quantitative PCR. Ctr mice had positive pVL within 2 weeks p.i. Rx mice challenged at 4 h and 24 h showed 100% protection and no detectable pVL throughout the 4 weeks of follow-up (P = 0.009; Mantel-Cox test). Mice challenged at 7 days were HIV-1 positive at 14 days p.i. Further, HIV-1 viral RNA (vRNA) in vaginal and spleen tissues of Rx group mice with negative pVL were examined using an in situ hybridization (ISH) technique. The detection of vRNA was negative in all Rx mice studied. The present studies elucidate TDF-NP-TMS gel as a long-acting, coitus-independent HIV-1 vaginal protection modality.

Development and validation of a simple and isocratic reversed-phase HPLC method for the determination of rilpivirine from tablets, nanoparticles and HeLa cell lysates.

In the present investigation, a simple and isocratic HPLC-UV method was developed and validated for determination of rilpivirine (RPV) from dosage forms (tablets and nanoparticles) and biological matrices like HeLa cell lysates. The separation and analysis of RPV was carried out under isocratic conditions using (a) a Gemini reversed-phase C18 column (5 µm; 4.6 × 150 mm) maintained at 35°C, (b) a mobile phase consisting of a mixture of acetonitrile and 25 m m potassium dihydrogen phosphate (in the ratio 50:50 v/v) at a flow rate of 0.6 mL/min and (c) atazanavir as an internal standard. The total run time was 17 min and the analysis of RPV and internal standard was carried out at 290 nm. The method was found to be linear (r(2) value > 0.998), specific, accurate and precise over the concentration range of 0.025-2 µg/mL. The lower limit of quantification was 0.025 µg/mL, the limit of detection was 0.008 µg/mL and the recovery of RPV was >90%. The stability of the RPV analytical method was confirmed at various conditions such as room temperature (24 h), -20°C (7 days), three freeze-thaw cycles and storage in an autosampler (4°C for 48 h). The method was successfully applied for the determination of RPV from conventional dosage forms like tablets, from polymeric nanoparticles and from biological matrices like HeLa cell lysates.

Development of phenyllactic acid ionic liquids and evaluation of cytotoxicity to human cervical epithelial cells.

Phenyllactic acid (PLA), is a naturally produced, broad-spectrum antimicrobial compound with activity against bacteria and fungi. PLA can be produced by a variety of lactic acid bacteria, including vaginal Lactobacillus species, which are healthy constituents of the vaginal microbiome with a protective role against invading pathogenic bacteria and/or fungi. Additionally, PLA has been shown to exhibit anti-inflammatory and immunomodulatory properties, overall indicating its therapeutic potential as an intravaginally delivered compound for modulation of the vaginal microbiome. However, PLA has low kinetic solubility in water. Hence, strategies to improve the solubility of PLA are necessary to facilitate its intravaginal delivery. Using biocompatible cations, choline and carnitine, we successfully transformed both d- and l-enantiomers of crystalline PLA into amorphous low-melting ionic liquids (ILs) with high water solubility. We further evaluated the in vitro cytotoxicity of PLA ILs to human cervical epithelial cells. Microscopic visualisation of cellular morphology using crystal violet staining and MTT cell proliferation assay revealed that PLA ILs result in minimal morphological changes and low cytotoxicity to human cervical epithelial cells. Overall, we successfully demonstrated that transforming PLA into ILs efficiently enhances its solubility in water and these formulations are not toxic to human epithelial cells. This investigation lays the groundwork for future testing of PLA ILs for their antimicrobial properties and metabolic activity within the cervicovaginal microenvironment.

Oral Self-Nanoemulsifying System Containing Ionic Liquid of BX795 Is Effective against Genital HSV-2 Infection in Mice.

BX795 is an emerging drug candidate that has shown a lot of promise as a next-generation non-nucleoside antiviral agent for the topical treatment of herpes simplex virus type-1 (HSV-1) and herpes simplex virus type-2 (HSV-2) infections. Our studies indicated that BX795 has limited oral bioavailability, which could be attributed to its low and pH-dependent solubility. Lipid-based formulations such as self-nanoemulsifying systems (SNESs) can improve the solubility and oral bioavailability of BX795, but the poor lipid solubility of BX795 further limits the development of SNES. To improve the loading of BX795 into SNES, we evaluated the ability of various bulky and biocompatible anions to transform BX795 into an ionic liquid (IL) with higher lipid solubility. Our studies showed that sodium lauryl sulfate and docusate sodium were able to transform BX795 into IL. Compared to pure BX795, the developed BX795 ILs showed differential in vitro cytocompatibility to HeLa cells but exhibited similar in vitro antiviral activity against HSV-2. Interestingly, BX795 docusate (BX795-Doc), an IL of BX795 with ∼135-fold higher lipid solubility than pure BX795, could be successfully incorporated into an SNES, and the developed BX795-Doc-SNES could readily form nanoemulsions of size ≤200 nm irrespective of the pH of the buffer used for dilution. Our in vitro studies showed that BX795-Doc-SNES retained the inherent antiviral activity against HSV-2 and showed similar in vitro cytocompatibility, indicating the availability of BX795 from the SNES in vitro. Finally, orally delivered SNES containing BX795-Doc showed a significant reduction in HSV-2 infection in mice compared to the untreated control. Thus, the transformation of BX795 into IL and the subsequent incorporation of the BX795 IL into the SNES are an effective strategy to improve oral therapy of genital herpes infection.

Tolerability, pharmacokinetics, and anti-herpetic activity of orally administered BX795.

Herpes simplex viruses type-1 (HSV-1) and type-2 (HSV-2) are ubiquitous human pathogens causing serious pathologies in the ocular, orofacial and anogenital regions. While current treatments such as nucleoside analogs are effective in most cases, the emergence of drug resistance necessitates the development of newer antivirals with different mechanisms of action. In this regard, BX795, a small molecule inhibitor has shown significant benefit in the treatment of herpesvirus infections previously when dosed topically. However, the efficacy of BX795's systemic dosage remains to be tested. In this study, we evaluated acute and short-term toxicity of orally administered BX795 at a concentration of 400 and 100 mg/kg respectively in mice. This was followed by an evaluation of pharmacokinetics and tissue distribution of BX795 on intravenous and oral administration. Based on these studies, we performed an in vivo antiviral study using murine models of ocular HSV-1 and genital HSV-2 infection. Our results indicate that orally administered BX795 is very well tolerated, had oral bioavailability of 56%, and reached ocular and genital tissues within the first 15 min of dosing. Our studies indicate that BX795 administered orally can significantly reduce herpesvirus replication in the ocular and genital tissue.

Characterization of soy polysaccharide and its in vitro and in vivo evaluation for application in colon drug delivery.

The objective of the present investigation was to establish potential of commercially available soy polysaccharide (Emcosoy®) for colon drug delivery. The soy polysaccharide-ethyl cellulose films were fabricated and characterized. The effect of the pectinase enzyme on the tensile strength and surface morphology of the film was evaluated. The permeation of chlorpheniramine maleate (CPM), a model hydrophilic drug from pectinase enzyme treated and untreated films was measured in pH 7.4 buffer. The soy polysaccharide-ethyl cellulose films were also incubated with Lactobacillus sp. culture for a specific duration, and effect on the CPM permeation was evaluated. The CPM capsules were coated with the soy polysaccharide-ethyl cellulose mixture, and Eudragit S100 was applied as a secondary coat. The coated CPM capsules were radiolabelled, and their in vivo transit was evaluated in human volunteers on oral administration. The pectinase enzyme had a significant influence on the tensile strength and surface morphology of the soy polysaccharide-ethyl cellulose films. The permeability of pectinase enzyme-treated and Lactobacillus sp.-treated films was significantly higher than that of untreated films. The CPM capsules were coated with the soy polysaccharide-ethyl cellulose mixture and Eudragit S100 and were successfully radiolabelled by a simple method. Gamma scintigraphic studies in human volunteers showed that the radiolabelled capsules maintained integrity for at least 9 h after oral administration. Thus, the soy polysaccharide has a potential in colon drug delivery.

Antifungal activity of alexidine dihydrochloride in a novel diabetic mouse model of dermatophytosis.

Dermatophytosis is one of the most prevalent fungal infections and a major public health problem worldwide. Recent years have seen a change in the epidemiological patterns of infecting fungi, corresponding to an alarming rise in the prevalence of drug-recalcitrant dermatophyte infections. In patients with diabetes mellitus, dermatophytosis is more severe and recurrent. The potency of promising new antifungal drugs in the pipeline must be expanded to include dermatophytosis. To facilitate this effort, we established a clinically pertinent mouse model of dermatophyte infections, in which diabetic mice were infected with Trichophyton mentagrophytes on abraded skin. The diabetic mouse model was optimized as a simple and robust system for simulating dermatophytoses in diabetic patients. The outcome of infection was measured using clinical and mycological parameters. Infected mice with fungal lesions were treated with oral and topical formulations of terbinafine or topical administration of the FDA-approved and repurposed pan-antifungal drug alexidine dihydrochloride (AXD). In this model, AXD was found to be highly effective, with outcomes comparable to those of the standard of care drug terbinafine.

Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.

Chronic inflammation of the immune privileged cornea originating from viral or nonviral conditions results in significant vision loss. Topical corticosteroids are the common treatments for corneal inflammation, but the drugs cause serious and potentially blinding side effects in the long term. Therefore, new standalone and/or synergistic anti-inflammatory therapies with lower side effects are desperately needed. Here, we show that the aromatic fatty acid phenylbutyrate (PBA) acts as a potent inhibitor of inflammation in preclinical ocular-inflammation models. PBA prevents the transcription as well as translation of pro-inflammatory cytokines by LPS and poly(I:C) via persistent inhibition of NF-κB signaling. PBA quickens the resolution of ocular inflammation in mice by decreasing corneal thickness and immune cell infiltration. More importantly, PBA can synergize with the dexamethasone to antagonize NF-κB signaling at lower drug concentrations. Our results demonstrate that PBA therapy exerts previously unreported anti-inflammatory effects in the eye and facilitates corneal healing during persistent inflammation.

Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review.

Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.

Hypo-osmolar rectal douche tenofovir formulation prevents simian/human immunodeficiency virus acquisition in macaques.

In spite of the rollout of oral pre-exposure prophylaxis (PrEP), the rate of new HIV infections remains a major health crisis. In the United States, new infections occur predominantly in men having sex with men (MSM) in rural settings where access to PrEP can be limited. As an alternative congruent with MSM sexual behavior, we have optimized and tested tenofovir (TFV) and analog-based iso-osmolar and hypo-osmolar (HOsm) rectal douches for efficacy against rectal simian/human immunodeficiency virus (SHIV) infection of macaques. Single TFV HOsm high-dose douches achieved peak plasma TFV levels similar to daily oral PrEP, while other formulations yielded lower concentrations. Rectal tissue TFV-diphosphate (TFV-DP) concentrations at the portal of virus entry, however, were markedly higher after HOsm douching than daily oral PrEP. Repeated douches led to significantly higher plasma TFV and higher TFV-DP concentrations in rectal tissue at 24 hours compared with single douches, without detectable mucosal or systemic toxicity. Using stringent repeated intrarectal SHIV exposures, single HOsm high-dose douches delivered greater protection from virus acquisition for more than 24 hours compared with oral PrEP. Our results demonstrate a rapid delivery of protective TFV doses to the rectal portal of virus entry as a potential low-cost and safe PrEP alternative.

Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery.

PURPOSE: To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. METHODS: The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. RESULTS: Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

Sulfobutyl ether(7) ß-cyclodextrin (SBE(7) ß-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity.

The objective of the present investigation was to study the ability of sulfobutyl ether(7)-ß-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether(7) ß-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether(7) ß-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether(7) ß-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether(7) ß-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.