Gihan Fetih

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000.

The aim of this study was to prepare and characterize solid dispersions of water insoluble non-steroidal anti-inflammatory drug, indomethacin (IND), with polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) for enhancing the dissolution rate of the drug. The solid dispersions (SDs) were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy (SEM), X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND-Gelu. and disappeared in case of higher ratio of IND-PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer (1:4) enhanced the drug solubility about 4-folds or 3.5-folds in case of SDs of IND-PEG or IND-Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures (PMs) or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer.

Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application

Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (Tgel), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The Tgel decreased with increasing PF-127 concentration. The Tgel was modulated by addition of PF-68 to be within the acceptable range of 25-37 °C. With increasing pluronic concentration, the in vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation. Razvoj i karakterizacija in situ gelirajućih pripravaka metronidazola na bazi pluronika za vaginalnu primjenu Cilj rada bio je razviti pripravke metronidazola (MTZ) za liječenje bakterijske vaginoze koji imaju sposobnost geliranja in situ, produljeno vrijeme zadržavanja na mjestu primjene, kontrolirano oslobađanje ljekovite tvari, povećanu učinkovitost te smanjiti ponovnu pojavu vaginoze i povećati suradljivost pacijenta. Pripravci koji geliraju in situ pripravljeni su koristeći različite koncentracije pluronika F-127 (PF-127), samog ili u kombinaciji s pluronikom F-68 (PF-68). Ispitivana je temperatura geliranja (Tgel) formulacija, in vitro oslobađanje ljekovite tvari, reološka svojstva, mukoadhezijska svojstva te kako ih podnaša vaginalna sluznica u slojevima tkiva. Uočeno je da se s povećanjem koncentracije PF-127 snižava Tgel. Dodatkom različitih količina PF-68 dobiveni su pripravci s rasponom Tgel od 25 do 37 ºC. S povećanjem koncentracije pluronika smanjilo se oslobađanje ljekovite tvari in vitro, a povećala se viskoznost i mukoadhezivnost. Histopatološ ka ispitivanja na zečicama ispitivane i kontrolne skupine dala su normalni histološ ki nalaz njihovih vagina i cerviksa. Na temelju in vitro evaluacije, formulacija s PF-127/PF-68 (20/10 %, m/m) izabrana je za daljnja klinička ispitivanja.

Colon-specific delivery and enhanced colonic absorption of [Asu1,7]-eel calcitonin using chitosan capsules containing various additives in rats

The objective of this study was to estimate the colon-specific delivery of [Asu1,7]-eel calcitonin (ECT) using chitosan capsules in rats. The intestinal absorption of ECT was evaluated by measuring the plasma calcium levels after oral administration of the chitosan capsules containing ECT and different combinations of additives. The same combinations were investigated by an in situ absorption experiment prior to in vivo administration of capsules. A marked decrease in plasma calcium levels was observed following the oral administration of chitosan capsules containing ECT, S-nitroso-N-acetyl-dl-penicillamine (SNAP), sodium glycocholate, bacitracin and aprotinin (pharmacological availability (PA)% = 6.344%), as compared with capsules containing only ECT (PA% = 0.551%) or capsules containing ECT with SNAP only (PA% = 1.651%). The hypocalcemic effect started 6–8 h after oral administration of capsules and sustained for 24 h. These findings suggest that colon-specific delivery of ECT can be achieved using chitosan capsules and these additives may be useful for improving the colonic absorption of ECT in rats.

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

Abstract The aim of this study was to develop liposomal-based (LBGF) and micro-emulsion-based (MBGF) gel formulations of croconazole to compare their topical delivery potential. Conventional gels were also prepared using various polymers such as sodium carboxymethyl cellulose (SCMC), Poloxamer 407, Carbopol 971P and chitosan. The in vitro release of croconazole from conventional gel formulations, LBGF and MBGF were carried out using cellophane membrane as permeation membrane. However, in vitro skin permeations studies of all formulations were carried out using rat skin. The results of the drug release/skin permeation studies indicated that the highest release was obtained from SCMC followed by chitosan, Poloxamer 407 and finally Carbopol 971P gel. Therefore, liposomes and micro-emulsions were loaded on Carbopol 971P gel. The drug release and skin permeation of croconazole from different LBGF and MBGF showed that MBGF had superior release/permeation than LBGF. MBGF having ethanol as co-surfactant showed higher release/permeation of drug than MBGF-containing propylene glycol. The analysis of data according to different kinetic models indicated that the release of drug from different LBGF and MBGF followed the Higuchi model. The antimicrobial activity of the different LBGF and MBGF of croconazole was carried out by measuring the inhibition zone (mm) and compared by the effect of miconazole cream as control. The different LBGF and MBGF showed an excellent activity against different species of fungi as compared with miconazole cream. Overall, these results indicated that developed LBGF and MBGF could have great potential for topical delivery of croconazole.

Preparation, charactarization and anti-inflammatory activity of celecoxib chitosan gel formulations

This study was designed to evaluate the suitability of chitosan polymer as a vehicle for topical delivery system. Celecoxib, which is a nonsteroidal anti-inflammatory drug, was incorporated into the gel vehicles in a concentration of 0.5 % w/v. Gels were prepared using three different concentrations and different molecular weights of chitosan. Viscosity, drug release from gels, permeation of drug through rat skin and anti-inflammatory activity of the drug were studied. In vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer using a pH of 6.8. The results showed that, the gel form containing 1.0 % w/v medium molecular weight chitosan has superior drug release than other forms, whilst the gel form containing 2.0 % w/v high molecular weight chitosan shows the lowest amount of drug release. The release data were treated with various kinetic principles to assess the relevant parameters. The results revealed an inverse correlation between the percent drug release and the polymer concentration used. The results also showed that the release of drug from the prepared gels obeyed the Higuchi’s diffusion model. The permeation of drug through rat skin was carried out. The flux of drug is independent on the viscosity of the formulae. The anti-inflammatory activity of the drug in different gel formulations was studied using carrageenan-induced rat paw edema method. The results obtained show that there is excellent anti-inflammatory activity of the gel forms on rat paw edema.

From The Mine to Cancer Therapy: Natural and Biodegradable Theranostic Silicon Nanocarriers from Diatoms for Sustained Delivery of Chemotherapeutics

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and pharmacodynamic evaluation

Abstract Non-ionic surfactant vesicles were prepared using Span-60 and cholesterol in the mass ratios of 1:1, 2:1, 1:2 and 3:1 for transdermal delivery of an anti-inflammatory drug meloxicam (MXM). The drug encapsulation efficiencies and particle size were observed in the range of 32.9–80.7% and 56.5–133.4 nm, respectively. Three different gel bases were also prepared using Poloxamer-407, Chitosan and Carbopol-934 as polymers to study the performance of the in vitro release of the drug. Prepared gels were also converted into niosomal gels. In vitro release characteristics of MXM from different gels were carried out using dialysis membrane in phosphate buffer (pH 7.4). The poloxamer-407 gel or niosomal poloxamer-407 gel showed the superior drug release over the other formulations. The release data were treated with various mathematical models to assess the relevant parameters. The results showed that the release of MXM from the prepared gels and niosomal gels followed Higuchi’s diffusion model. The flux of MXM was found to be independent on the viscosity of the formulations. The anti-inflammatory effects of MXM from different niosomal gel formulations were evaluated using carrageenan-induced rat paw edema method, which showed superiority of niosomal gels over conventional gels.

Doxycycline in the treatment of bleeding with DMPA: a double-blinded randomized controlled trial

BACKGROUND Increased matrix metalloproteinase (MMP) activity in the endometrium is a predisposing factor for bleeding with depot medroxy progesterone acetate (DMPA) injectable contraception. Doxycycline (DOX) has been proven in vitro to inhibit MMP-mediated degradation of stromal matrix. The current study examined the effect of DOX compared to placebo in treating a current bleeding episode during DMPA use. STUDY DESIGN A double-blinded randomized controlled trial was conducted in Assiut, Egypt. DMPA users with current bleeding episode were counseled to participate. Women who agreed to participate were randomly assigned to receive 100 mg DOX twice daily for 5 days (34 patients) or an identical placebo (34 patients). All participants were asked to report bleeding and spotting days in a menstrual diary. All participants were followed for 3 months after treatment. This trial was registered (NCT01254799). RESULTS The relative risk to stop a bleeding episode within 10 days of starting treatment was 0.88 (confidence interval 0.64-1.21) in the treatment group compared to the control. DOX treatment caused no significant difference compared to placebo in the number of bleeding and/or spotting days in the 3 months following the treatment. CONCLUSION Doxycycline as MMP inhibitor is not effective in stopping a current attack of bleeding with DMPA. It also does not improve the bleeding characteristics of women for the subsequent 3 months following the treatment.

Liposomal gels for site-specific, sustained delivery of celecoxib: in vitro and in vivo evaluation.

Preclinical Research

Pilot randomized trial for treatment of bacterial vaginosis using in situ forming metronidazole vaginal gel

Aim:  To compare the efficacy of a novel vaginal delivery system for metronidazole (0.8% MTZ in situ gel) versus a conventional MTZ vaginal gel product in the treatment of bacterial vaginosis (BV).