Triamcinolone-loaded self nano-emulsifying drug delivery systems for ocular use: An alternative to invasive ocular surgeries and injections.

Inflammation of the posterior segment of the eye is a severe condition and hard to cure as delivery of drugs to the inflammation site is inefficient. Currently, the primary treatment approach is ocular surgery or invasive ocular injections. Herein, we designed and developed a topically self nano-emulsifying drug delivery system (SNEDDs) to deliver triamcinolone acetonide (TCA) to the posterior segment of the eye. A screening based on TCA solubility was conducted on each excipient followed by preparation of various formulations using different ratios of the selected excipients. Vesicles of optimized SNEDDs had less than 100 nm size and spherical morphology. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed self-emulsified vesicles have relatively high safety on retinal pigment epithelium (RPE) cell line. Furthermore, efficient cellular uptake of coumarin 6-loaded SNEDDs in RPE using confocal laser scanning microscopy (CLSM) was confirmed. In addition, an in-vivo study using hematoxylin and eosin (H&E) staining revealed that 14 days of topical treatment of albino rabbit eyes with TCA-loaded SNEDDs was safe and no sign of tissue destruction and inflammation was detected in different parts of the eye sections including cornea, sclera, retina, and optic nerve. Also, the CLSM images from topically treated eyes with coumarin 6 (a hydrophobic, fluorescent drug model) loaded SNEDDs, showed that the optimized SNEDDs could properly penetrate toward the posterior segments of the eye especially the retina, posterior parts of the choroid, and sclera. Considering the outstanding results obtained by ocular tissue penetration and low toxicity, prepared SNEDDs, have the potential to be used as a topical administration for treating posterior segment disorders of the eye through an utterly non-invasive route and TCA-loaded SNEDDs could be an alternative for TCA intravitreal and intra conjunctival injections.

Determination of Cleaning Limits Considering Toxicological Risk Evaluation to Minimize the Risk of Cross Contamination.

The historical approaches that have been used to establish cleaning validation acceptance limits should be updated to recent approaches to prevent cross contamination. In the present investigation, a cleaning method was validated using high performance liquid chromatography. Method modification critical parameters including spiking, swab sampling from PVC, Stainless Steel, and Polyethylene, extraction technique from swab, solubility, potency, toxicity (LD50), and improvement of limit of detection (LOD) of the method through analytical method validation were studied. In addition, roughness, mechanical and electro-polishing, consideration of dosage form as a quantitative factor, acceptable daily exposure (ADE), and permitted daily exposure (PDE) in the worst-case determination were considered in the study. The method was validated based on USP and ICH guidelines for specificity, limit of detection, limit of quantitation, precision, accuracy, linearity, and range. Linear regression analysis of data for the calibration plot in the range of 7.43, 10.89, 21.78, 43.56, 87.12 µg/mL, and relative standard deviation (R.S.D.) found to be 0.5, 0.4, 0.2, and 0.2, respectively with correlation coefficient of R2 = 0.999997. The LOD and the limit of quantitation (LOQ) were 2.23 and 7.43 µg/mL, respectively. Good recoveries in the range of 73.65-81.20%, and precision with relative standard deviation values lower than 15% have been obtained. The proposed method developed for cleaning validation is specific, precise, and useful for determination of cleaning acceptance limits using health-based limit and Quality Risk Management to develop an appropriate cleaning program for engineering design, safety of patients, and worker protection.

Evaluation of Swab and Rinse Sampling Procedures and Recovery Rate Determination in Cleaning Validation Considering Various Surfaces, Amount and Nature of the Residues and Contaminants.

A cleaning validation for a family of compounds utilizing swab sampling and rinse solution procedures, and high performance liquid chromatography for separation and detection of the analytes was performed.Effective parameters on recovery including sampling method, swab characteristics, solvent, swabbing technique, and material substance of product contact surfaces within the manufacturing equipment for swab and rinse sampling method, quantitative cleaning verification method, and active pharmaceutical ingredient (API) level and nature have been studied.The limit of detection and the limit of quantitation for the HPLC method were determined to be 0.0198 µg/mL, and 0.0495 µg/mL of the analyte, respectively. The linearity on replicate injections of the standard prepared in the range of 0.78, 1.55, 3.1, and 6.2 µg/mL, and relative standard deviation (R.S.D.) found to be 1.2, 1.0, 0.9, and 0.6, respectively with correlation coefficient of R2 = 0.9999. Recovery coverage for each type of surface was acceptable, ranging from 63.88% for swab sampling of stainless steel to 97.85% for rinse sampling of PVC. The acceptance criteria for precision on replicate injections of the analyte prepared in three concentration levels covering the specified range of 50, 100, and 200% was successfully accomplished R.S.D. lower than 15% for recovery results.Thus, choosing the appropriate sampling method, swab type, and surface condition can affect and increase recovery rate determination efficiency.

The efficacy and safety of permethrin 2.5% with tea tree oil gel on rosacea treatment: A double-blind, controlled clinical trial.

BACKGROUND: Rosacea is a chronic skin condition that typically affects the face and it results in redness and inflammation. The main risk factors of this disease are Demodex folliculorum, living in the pilosebaceous units. AIMS: To evaluate the efficacy and safty of permethrin 2.5% in combination with tea tree oil (TTO) topical gel versus placebo on Demodex density (Dd) and clinical manifestation using standard skin surface biopsy (SSSB) in rosacea patients. PATIENT/METHODS: In this double-blind, randomized clinical trial, 47 papulopustular rosacea patients were enrolled, with 35 patients finishing the 12 weeks of treatment. Each patient used permethrin 2.5% with TTO on one side of the face and a placebo on the other, twice daily for 12 weeks. SSSB, photography and clinical rosacea scores according to National Rosacea Society, as well as adverse drug reaction (ADRs) were reported at the baseline, 2nd, 5th, 8th, and 12th weeks. RESULTS: A total of 47 patients were enrolled with papulopustular rosacea, and 35 patients finished the study. The effects of permethrin 2.5% with TTO gel on mite density were significant at week 5, 8, 12 (P value = .001). Clinical features and global assessments showed papules, pustules and nontransient erythema had improvement in drug group after 12 weeks (P values <.05). The improvement of burning and stinging and dry appearance was greater than the placebo gel (P value <.05). Itching in placebo group was significantly more than other group (P value = .002). CONCLUSION: Administration of permethrin 2.5% with TTO gel demonstrated good efficacy and safety in rosacea. This topical gel inhibited the inflammatory effects of rosacea and reduced Demodex mite.

A Novel High Performance Liquid Chromatographic Method for Determination of Nystatin in Pharmaceutical Formulations by Box-Behnken Statistical Experiment Design.

In this study a novel High Performance Liquid Chromatography for the assay of nystatin in oral and vaginal tablets were optimized and validated using Box-Behnken experimental design. The method was performed in the isocratic mode on a RP-18 column (30 °C) using a mobile phase consisting of ammonium acetate 0.05 M buffer/ Methanol mixture (30:70) and a flow-rate of 1.0 mL/min. The specificity, linearity, precision, accuracy, LOD and LOQ of the method were validated. The method was linear over the range of 5-500 µg/mL with an acceptable correlation coefficient (r(2) = 0.9996). The method's limit of detection (LOD) and quantification (LOQ) were 0.01 and 0.025 µg/mL respectively. The results indicate that this validated method can be used as an alternative method for assay of nystatin.