Effect of misoprostol versus oxytocin on delivery outcomes after labour induction in pregnant women: A systematic review and meta-analysis of randomized controlled trials.

A large number of randomized controlled trials (RCTs) have been published on the effects of oral/vaginal misoprostol and oxytocin on delivery outcomes; however, data from these RCTs are conflicting. Although some meta-analyses summarized available findings in this regard, several eligible RCTs have been published since the release of those meta-analyses. Therefore, the current updated systematic review and meta-analysis of RCTs was conducted to compare the effects of oral/vaginal misoprostol and oxytocin on delivery and neonatal outcomes. A systematic search, using relevant keywords, was done in the online databases of PubMed/Medline, Scopus, and ISI Web of Science, up to April 2023, to identify eligible articles investigating the effect of oral/vaginal misoprostol and oxytocin on delivery outcomes including maternal [cesarean/vaginal delivery within 24 h after labour induction, Tachysystole, hypertonicity, hyper-stimulation, postpartum hemorrhage (PPH)] and neonatal outcomes [mean Apgar score, admission to neonatal intensive care unit (NICU), and death]. In total, 45 RCTs with a total sample size of 8406 participants were included. Meta-analysis revealed that vaginal misoprostol administration, compared with oxytocin, resulted in a significant reduction in the rate of cesarean and a significant increase in the rate of vaginal delivery and Tachysystole risk. Also, oral misoprostol was associated with a significant reduction in the rate of cesarean and a significant increase in the risk of hypertonicity compared with oxytocin. However, oral misoprostol had no significant effect on vaginal delivery compared with oxytocin. For other outcomes including hyper-stimulation, perinatal death, NICU admission, and mean Apgar score among newborns, we found no significant difference between oral/vaginal misoprostol and oxytocin. In total, vaginal/oral misoprostol might be a better method for labour induction compared with oxytocin. PROSPERO registration: CRD42023412325.

Economic Burden of Multiple Sclerosis Drugs in Iran during 2011-2019.

Background: Due to the invariably progressive nature of multiple sclerosis (MS) and the high economic burden of chronic diseases, this study was performed to estimate the economic burden of MS medications in Iran. Methods: The present research is a descriptive study performed using comprehensive national data of Iran's Health Insurance Organization (IHIO). The timeframe for study was 2011-2019. In order to calculate the economic burden of MS medications, the cost of illness (COI) method based on the prevalence approach was used. In this study, economic burden estimation was performed according to available data on medication costs. Data mining was also used to perform different stages of study. Results: The number of patients receiving MS medications covered by IHIO has increased from 19,367 in 2011 to 50,642 in 2019. The economic burden of MS medications of patients covered by the IHIO increased from $81 million to $96 million between 2011 and 2019, respectively. Among the 9 medications studied, Interferon accounted for a very high share of costs in all years. The cost per patient receiving medication has also increased from $7,000 in 2011 to $18,000 in 2019. Conclusion: Calculations of the economic burden of MS medications in Iran showed an upward trend during the 9 years of the study, which due to the increasing number of patients in Iran, the arrival of new medications and also the increase in prices.

Pharmaceutical and clinical studies of celecoxib topical hydrogel for management of chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) can be categorized as a frequent dose-limiting side effect following administration of chemotherapeutic agents, which needs an effective medication to avoid dose reduction or discontinuation. Oral celecoxib has been proved to be the best pharmacological intervention to ameliorate the skin lesions. However, due to reported gastrointestinal and cardiovascular toxicity following its long-term administration, celecoxib topical application would be a safe alternative for skin disorders. In this work, first, we formulated and optimized a topical hydrogel of celecoxib (1%) and then we investigated its efficacy in the management of chemotherapy-induced HFS in cancer patients. Optimized hydrogel showed acceptable results for drug content, pH, rheology, and stability. Analyzing in vitro drug release study by various mathematical models, the optimized hydrogel showed a zero-order release pattern with 93.27 ± 1.56% cumulative celecoxib release within 8 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of celecoxib for topical delivery. Twenty-nine patients suffering from HFS were randomized to receive celecoxib and the placebo hydrogels 2 times a day for 3 weeks. At the baseline and at the end of the trial, HFS grades were determined. No serious adverse events occurred in patients who completely followed the instructions. No statistically significant differences between two arms were observed at the baseline (p value = 0.38). By contrast, Wilcoxon signed-rank test showed significant differences when secondary grades (p value = 0.05) and grade differences (p values < 0.001) were analyzed. Overall, the study proved that celecoxib hydrogel could be a promising intervention to manage HFS side effect.

Estimation the medical cost of multiple sclerosis in Iran; 2019-2020.

BACKGROUND: Due to the high and increasing economic burden of chronic diseases, including Multiple sclerosis (MS), we aimed to investigate the medical cost of MS in Iran. METHODS: This is a descriptive cross-sectional study which conducted using comprehensive national prescription data from Iran's Health Insurance Organization (IHIO) and rehabilitation data from Ministry of Health and Iran Welfare Organization. The time period considered for this study was 2019-2020. In order to calculate the medical cost of MS, the cost-of-illness (COI) method was used based on the prevalence-based approach and the cost of medications, determining and diagnosing the MS risk, follow-up and rehabilitation was estimated. RESULTS: The total medical cost of MS in Iran in 2019-2020 was estimated at $238,124,160, which medications and rehabilitation services had the largest share in the medical cost of MS in Iran with 80 and 19%, respectively, and the cost share of determining and diagnosing of the disease risk accounted for about less than 1%. The total medication cost was estimated to be equal to $192,298 thousand. The total cost of determining and diagnosing of the MS risk was estimated at $348,574 and the total cost of rehabilitation services for all MS subgroups in 2019-2020 was estimated at $45,477,205. CONCLUSIONS: Results of calculating the medical cost of MS in Iran in 2019-2020 showed a significant burden on the Iranian health care system and society, among which the medication cost had the largest share, which requires serious attention of health system policymakers.

Efficacy of topical Lawsonia inermis L. (Henna) hydrogel in fluorouracil-induced hand-foot syndrome: a pilot randomized double-blind placebo-controlled clinical trial.

PURPOSE: Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of fluoropyrimidine drugs like capecitabine and 5-flourouracil (5-FU) in breast and gastrointestinal cancers. It has been shown that conventional application of Lawsonia inermis L. (Henna) is effective in ameliorating of the skin lesions. To increase the patient compliance, in this study we formulated a standardized topical hydrogel (H.gel) containing the hydroalcoholic extract (10%) of Henna and evaluated its clinical efficacy for the management of fluorouracil associated HFS. MATERIAL AND METHODS: The topical dosage form was standardized based on its Lawsone content. Eighteen patients suffering from HFS were randomized to receive H.gel and the placebo four times a day for 2 weeks. At the baseline and at the end of the trial, HFS grades were determined. RESULTS AND CONCLUSIONS: Allergic reactions following administration of H.gel were observed in one patient, while no serious adverse events occurred in the others. No statistically significant differences between two arms were observed at the baseline (p-value = 0.133), after treatment (p-value = 0.590) and grade differences (p-value = 0.193). The applied hydrogel showed less efficacy compared to the traditional method of using Henna, meaning that Lawsone may not be a good indicator for standardizing the topical dosage form.

Effect of monoterpenes on ex vivo transungual delivery of itraconazole for the management of onychomycosis.

BACKGROUND: Onychomycosis, a fungal nail infection, is an important problem as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions. Systemic treatment of onychomycosis presents safety issues due to possible drug-drug interactions and severe side effects. Although topical therapy of onychomycosis is advantageous due to its localized effect, the efficacy of such therapy depends on achieving effective concentrations of antifungal agents at the infection site. An approach to reach to this end would be driving benefit from synergic activity of antifungal agents for example itraconazole and monoterpenes. However, because of low transungual penetration of itraconazole, a molecule with high molecular weight and very low water-solubility, the effect of the latter compounds on itraconazole nail delivery should be investigated, which was the aim of this study. METHODS: Ex vivo permeation experiments were carried out through soaking the nail clippings of ten healthy volunteers in control and working solutions containing itraconazole (1 mg mL-1 ) and itraconazole (1 mg mL-1 ) plus 6% of each monoterpene including camphor, eucalyptol, menthol, and thymol, respectively, for 36 hours. The amount of itraconazole in nail clippings was quantified hereafter using a validated HPLC method. RESULTS: Statistical analysis showed that itraconazole transungual permeation was not influenced by the studied monoterpenes (P value > .05). CONCLUSION: These results provided a new perspective for designing topical dosage forms for the treatment of onychomycosis.

Fabrication and In-vitro Evaluation of Buccal Mucoadhesive Tablet of Meloxicam.

In this study, buccal mucoadhesive tablets of meloxicam were formulated for drug delivery as an alternative route. Direct compression method was applied for the preparation of tablets. Also, different polymers, including hydroxypropyl methyl cellulose (HPMC) 1000, 4000, and 10000, as well as carbopol 934p and carbopol 971p were used as the mucoadhesive polymer and retardant polymer. Thirteen formulations were investigated with various concentrations of polymers. The physicochemical characteristics, in-vitro drug release, swelling index, and taste modification of tablets were evaluated. Also, Carr's index and Hausner ratio were studied. In addition, zero-order, first-order, and Higuchi kinetics were investigated and the results showed that the highest correlation coefficient (R2) is related to zero-order kinetic for formulations B2 and B3. Furthermore, the highest R2 is related to Higuchi kinetic for formulation C3. Formulation B2 showed the maximum release of 99% in 12 h. The results demonstrated that Formulation B2 can be considered as a proper buccal mucoadhesive tablet of meloxicam with desired property.

Design and Evaluation of Ocular Controlled Delivery System for Diclofenac Sodium.

Diclofenac sodium as ophthalmic dosage form is used for the treatment of the pain, swelling and redness of patients' eyes recovering from cataract surgery; however, it faces the bioavailability limitation of eye drops due to effective protective mechanisms and corneal barrier functions in the eyes. Therefore, this investigation was aimed to develop ocular film formulations to achieve controlled drug release. Drug films were prepared using polymers, namely hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP), Eudragit RL PO, and Eudragit RS PO by solvent casting method considering parameters such as drug: polymer ratio, different polymer combinations as well as plasticizer effect. Ocular films were evaluated for various physicochemical parameters such as physical characters, film thickness, uniformity of weight, drug content, swelling index, mucoadhesion time and in-vitro release study. Ocular films complied with all physicochemical parameters underwent in-vitro release study. Finally, the film formulation with HPMC: Eudragit RS PO 1:1 ratio, Drug: Polymer ratio 1:45 and glycerin as plasticizer showed controlled and prolonged release following the zero order and non-Fickian transport.

Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet.

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation.