Nilüfer Tarimci

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ψ

Objectives  Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (β‐CD) is investigated in 66 acne vulgaris patients.

Use of cyclodextrins as a cosmetic delivery system for fragrance materials: Linalool and benzyl acetate

The aim of this study was to increase the stability and water solubility of fragrance materials, to provide controlled release of these compounds, and to convert these substances from liquid to powder form by preparing their inclusion complexes with cyclodextrins (CDs). For this purpose, linalool and benzyl acetate were chosen as the fragrance materials. The use of β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) for increasing the solubility of these 2 fragrance materials was studied. Linalool and benzyl acetate gave a B-type diagram with βCD, whereas they gave an AL-type diagram with 2-HPβCD. Therefore, complexes of fragrance materials with 2-HPβCD at 1:1 and 1:2 molar ratios (guest:host) were prepared. The formation of inclusion complexes was confirmed using proton nuclear magnetic resonance (1H-NMR) spectroscopy and circular dichroism spectroscopy. The results of the solubility studies showed that preparing the inclusion complex with 2-HPβCD at a 1:1 molar ratio increased the solubility of linalool 5.9-fold and that of benzyl acetate 4.2-fold, whereas the complexes at a 1:2 molar ratio increased the solubility 6.4- and 4.5-fold for linalool and benzyl acetate, respectively. The stability and in vitro release studies were performed on the gel formulations prepared using uncomplexed fragrance materials or inclusion complexes of fragrance materials at a 1:1 molar ratio. It was observed that the volatility of both fragrance materials was decreased by preparing the inclusion complexes with 2-HPβCD. Also, in vitro release data indicated that controlled release of fragrances could be possible if inclusion complexes were prepared.

Microparticulate Based Topical Delivery System of Clobetasol Propionate

Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the worlds population. Clobetasol propionate which is a superpotent topical corticosteroid is widely used for topical treatment of psoriasis. Conventional dosage forms like creams and ointments are commonly prefered for the therapy. The purpose of this study was to develop a new topical delivery system in order to provide the prolonged release of clobetasol propionate and to reduce systemic absorption and side effects of the drug. Clobetasol propionate loaded-poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by oil-in-water emulsion–solvent evaporation technique. Particle size analysis, morphological characterization, DSC and XRD analyses and in vitro drug release studies were performed on the microparticle formulations. Emulgel formulations were prepared as an alternative for topical delivery of clobetasol propionate. In vitro drug release studies were carried out from the emulgel formulations containing pure drug and drug-loaded microspheres. In addition, the same studies were performed to determine the drug release from the commercial cream product of clobetasol propionate. The release of clobetasol propionate from the emulgel formulations was significantly higher than the commercial product. In addition, the encapsulation of clobetasol propionate in the PLGA microspheres significantly delayed the drug release from the emulgel formulation. As a result, the decrease in the side effects of clobetasol propionate by the formulation containing PLGA microspheres is expected.

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium.

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60–80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.

Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion - Solvent evaporation method.

With Quality by Design (QbD), a systematic approach involving design and development of all production processes to achieve the final product with a predetermined quality, you work within a design space that determines the critical formulation and process parameters. Verification of the quality of the final product is no longer necessary. In the current study, the QbD approach was used in the preparation of lipid nanoparticle formulations to improve skin penetration of 5-Fluorouracil, a widely-used compound for treating non-melanoma skin cancer. 5-Fluorouracil-loaded lipid nanoparticles were prepared by the W/O/W double emulsion - solvent evaporation method. Artificial neural network software was used to evaluate the data obtained from the lipid nanoparticle formulations, to establish the design space, and to optimize the formulations. Two different artificial neural network models were developed. The limit values of the design space of the inputs and outputs obtained by both models were found to be within the knowledge space. The optimal formulations recommended by the models were prepared and the critical quality attributes belonging to those formulations were assigned. The experimental results remained within the design space limit values. Consequently, optimal formulations with the critical quality attributes determined to achieve the Quality Target Product Profile were successfully obtained within the design space by following the QbD steps.

Sustained release characteristics and pharmacokinetic parameters of ketoprofen suppositories using chitosan

Abstract The use of chitosan granules as a means of achieving sustained release of ketoprofen (KP) in suppository form was examined. The suppositories were prepared using different molecular weight polyethylene glycol in various portions. In contrast with the rapid release of conventional suppository form, sustained release form chitosan granules were observed. Furthermore, the release rate could be controlled by changing the mixing ratio of drug and chitosan. The potential of a suppository which has chitosan granules of KP was compared with a conventional form in rabbits. When a conventional suppository was administered rectally, the plasma concentration reached the maximum level in 1 h. The sustained release form also reached the maximum level in the same time but, produced a sustained plateau of the drug. This is due to the slow rate of release and a longer residence time in the rectum. However, the sustained release formulation reduces the rectal bioavailability by nearly 40%, in comparison with the conventional formulation.

Topical emulgel formulation containing inclusion complex of calcipotriol with cyclodextrin

Psoriasis is a relatively common, chronic, inflammatory disease that affects the skin, scalp, and joints. Calcipotriol is one of the most commonly used topical agents for the treatment of psoriasis. However, it is a water-insoluble active substance and frequently leads to skin irritation in patients. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of (α-1,4-)-linked d-glucopyranose units. CD molecules have a hydrophilic outer surface and a lipophilic central cavity, and they are able to form inclusion complexes in aqueous solutions with many drugs. They can increase bioavailability, aqueous solubility, and stability and also reduce the side effects of the drugs. The aim of this study was to develop a new topical drug delivery system of calcipotriol in order to improve the solubility and dissolution characteristics of the drug and reduce the undesirable side effects. For this purpose, an inclusion complex of calcipotriol with Captisol® was prepared, and complex formation was confirmed. The inclusion complex and pure drug were formulated separately in an emulgel base. Dissolution profiles of calcipotriol from emulgel formulations were compared with a commercial product of the drug. The drug release was significantly increased with the emulgel formulations compared to the commercial cream product.

Studies on Sustained Release Iii: Matrix Granules of Sulfamethizole

AbstractPolymethylmethacrylate and cellulose acetate phtalate has been employed for the preparation of matrix sustained release sulfamethizole granules. The effect of various adjuvants on the release profile is also investigated. It is seen that, this type of sustained release is suitable for high values of release rate in contrast to inert matrix type tablets. The kinetics of release is not zero order, but RRSBW distribution seems to give better fits. Cellulose acetate phtalate warrants further work in such formulations; possibly with the concurrent employment of other polymers.

An objective analysis of sebum, pH and moisture levels of the external ear canal skin

OBJECTIVE To determine sebum, pH and moisture levels of external ear canal skin, and compare the patients who complain of ear itching and the normal population for these parameters. And evaluate the improvement subjectively in the ones given dexamethasone sodium phosphate (DSP) cream or placebo-water in oil emulsion type cream, and to determine the changes in sebum, pH and moisture levels after the treatment. METHODS 32 females with the complaint of isolated external ear canal itching and 42 healthy women were included in this randomized prospective controlled study. The sebum, pH and moisture levels of ear skin of the patients and the controls were determined from baseline and following treatment. Patients used DSP in their right and the placebo in their left ears for 15 days. Subjective analysis of itching level was measured at baseline, and on 15th and 30th days using visual analog scale (VAS). RESULTS There was no statistically significant difference between pretreatment and post-treatment pH and sebum levels of the study group and the control group. However, pretreatment and post-treatment moisture levels of the study group were significantly higher (p<0.001). CONCLUSION The study found an association of increased moisture levels of the external ear canal skin and isolated ear itching.

Development of a HILIC method for the determination of 5-fluorouracil from nano drug delivery systems and rat skin extracts

HIGHLIGHTSFirst hydrophilic interaction liquid chromatography with diode array detection study for stability indicating determination of 5‐Fluorouracil.5‐Fluorouracil loaded solid lipid nanoparticle and nano lipid carrier formulations were developed.Developed method has sufficient sensitivity for the estimation of 5‐Fluorouracil in raw materials, marketed formulation and rat skin extracts.Ex‐vivo Penetration/Permeation Studies with rat skin indicated that higher dermal accumulation of 5‐Fluorouracil was obtained with nano lipid carrier formulation. ABSTRACT This is the first report in literature using hydrophilic interaction liquid chromatography (HILIC) in combination with diode array detector (DAD) for stability indicating determination of 5‐Fluorouracil (5‐FU) from its bulk form, pharmaceutical preparations, developed solid lipid nanoparticle (SLN) and nano structured lipid carrier (NLC) drug delivery systems as well as the rat skin extracts. The separation was performed at 45°C, on Sequant Zic HILIC (250mm×4.60mm ID, 5&mgr;m, 200Ao), peek HPLC column. Mobile phase is consisting of a mixture of acetonitrile: buffer containing 5mM ammonium acetate (95:5; v/v). The pH of the mobile phase was adjusted to 7.0 using 1M NaOH. The analysis was carried out at 0.75mLmin−1 flow rate with a detection wavelength of 265nm and the injection volume was arranged as 10&mgr;L. The developed method was fully validated in accordance with the International Council on Harmonization (ICH) Guidelines. Specificity of this method was demonstrated by forced degradation studies. As a result of calibration studies, the calibration curve was found linear in the concentration range of 1–250&mgr;gmL−1 (R2=0.999). The precision of this technique calculated within the frame of intra‐day and inter‐day based on a percentage of relative standard deviation (RSD%) values (<2%). The limits of detection and quantification were 11 and 37ngmL−1 respectively. On the other hand, 5‐FU loaded SLN and NLC formulations with average particle size of 370nm were also developed and compared in order to increase the permeation of drug into the rat skin. Ex‐vivo Penetration/Permeation Studies indicated that higher dermal accumulation of 5‐FU was obtained with NLC formulation. As a conclusion, the present work expressed the optimization and the validation of a selective, simple, precise and accurate fully validated HILIC method with sufficient sensitivity for the estimation of 5‐FU in raw materials, marketed formulation and rat skin extract after applying both of the commercial product and newly developed nanoparticulate drug delivery systems on to the rat skins with high percentage recoveries.