Solubility and Thermodynamic Analysis of Isotretinoin in Different (DMSO + Water) Mixtures.

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H2O) (2)} combinations were studied at 298.2-318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the "van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". In mixtures of {(DMSO (1) + H2O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10-1 at 318.2 K) and lowest in pure H2O (3.14 × 10-7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was "endothermic and entropy-driven" in all of the {(DMSO (1) + H2O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H2O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H2O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H2O.

Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding.

BACKGROUND: Vincristine is a vital constituent of chemotherapeutic regimens. Vincristine-induced neuropathy is a challenging adverse effect that impacts quality of life and treatment course. The dose rounding of chemotherapies is a strategy that is commonly used in clinical practice. Nevertheless, the frequency of developed neuropathy in vincristine first-time users and the potential association with dose rounding remains elusive. METHODS: A retrospective analysis was conducted on patients administered vincristine for the first time between 2016 and 2022 using the King Saud University Medical City (KSUMC) database. Patients were stratified into pediatric and adult groups. Neuropathy frequency, its association with demographic and clinical parameters, and the Impact of dose rounding were assessed using SPSS software version 28. RESULTS: Approximately 34.6% of patients were diagnosed with neuropathy after vincristine administration. Autonomic neuropathy was common among affected adults and pediatric patients (55.1% and 56.1%, respectively), while cranial neuropathy was more frequent in pediatric patients. Higher BSA (p = 0.038) and Scr (p = 0.044) in the pediatric group, the presence of respiratory comorbidities (p = 0.044), and the use of azole antifungals (p < 0.001) in the adult group were significantly associated with neuropathy episodes. The rounding-up of vincristine doses was significantly associated with increased neuropathy occurrence (p < 0.001), while dose rounding-down was significantly associated with a decrease in neuropathy in both groups of patients (p < 0.001). CONCLUSIONS: Our findings demonstrate that autonomic neuropathy is the most common vincristine-related neuropathy, regardless of the patient's age. Dose rounding is a significant determinant of vincristine-induced neuropathy in both groups. Further studies are needed to evaluate the variables that exacerbate or prevent neuropathy associated with the first-time use of vincristine.

Environmentally friendly stability-indicating HPLC method for the determination of isotretinoin in commercial products and solubility samples.

In this study, an environmentally friendly "high-performance liquid chromatography (HPLC)" assay to quantify isotretinoin (ITN) in commercial products and solubility samples is designed and verified. A Nucleodur reverse-phase C18 column was used as the stationary phase to identify ITN. The ecologically friendly mobile phase was composed of ethyl acetate and ethanol (50:50 v/v), and it was delivered at a flow rate of 1.0 mL/min. ITN was measured at 354 nm in wavelength. The current HPLC method had a determination coefficient of 0.9994 and was linear in the 0.2-80 µg/g range. The current protocol for ITN measurement was also rapid (retention time = 2.78 min), accurate (%recoveries = 98.60-101.52), precise (% uncertainties = 0.71-0.98), and sensitive. According to the AGREE methodology, the current procedure received an outstanding greenness profile with an AGREE score of 0.76. By determining ITN in commercial products and solubility samples, the applicability of the current approach was proven. ITN was discovered to be present in 98.43% and 100.84%, respectively, of commercial capsule brands A and B. The ITN's solubility in numerous eco-friendly solvents was successfully measured. Under different stress conditions, the current approach was able to distinguish between its degradation products, demonstrating its stability-indicating characteristics. These findings indicated that ITN in procured capsules and solubility samples might be regularly tested by the suggested approach.

The Impact of Cancer Relapse and Poor Patient Outcomes on Health Care Providers Practicing in the Oncology Field.

INTRODUCTION: Devastating cancer-related events are not uncommon, and these events have weakened communication performance and induced stress among health care providers (HCPs), particularly physicians. This study aimed to investigate the perspective of HCPs emotionally affected by poor clinical outcomes due to the failure of cancer therapy. METHODS: A cross-sectional, online survey was conducted over 3 months among HCPs practicing in the field of oncology in Saudi Arabia, comprising physicians, pharmacists, and nurses. Data were analyzed using Statistical Package for Social Sciences version 26.0. A P-value <.05 was considered statistically significant. RESULTS: This study demonstrated a positive correlation between HCPs' length of experience and emotional impact of treatment failure, albeit this was not statistically significant (P = .071). Analysis of their perspective toward failure of cancer therapies revealed a significant impact of occupation and sex (P = .014 and P = .047, respectively). Moreover, occupation played a significant role in shaping the viewpoint of HCPs toward the need for conducing further research to test the appropriateness of treatment protocols on local patients (P = .022). Despite the emotional responses of HCPs to suboptimal clinical outcomes, factors such as work burnout, lack of concentration and patience, work or personal problems, and under appreciation were frequently identified as triggers of such outcomes. CONCLUSION: Our results revealed that poor clinical outcomes observed among cancer patients are emotional triggers for HCPs practicing in the oncology field. The emotional response is often perceived negatively, and can potentially lead to a decline in the quality of care provided to these patients.

A practical method for oral administration of isotretinoin in pediatric oncology patient: A case study of neuroblastoma.

INTRODUCTION: Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only. CASE REPORT: A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug. MANAGEMENT AND OUTCOMES: The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass. DISCUSSION: To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended.

Solubilization and Thermodynamic Analysis of Isotretinoin in Eleven Different Green Solvents at Different Temperatures.

The solubilization and thermodynamic analysis of isotretinoin (ITN) in eleven distinct green solvents, such as water, methyl alcohol (MeOH), ethyl alcohol (EtOH), 1-butyl alcohol (1-BuOH), 2-butyl alcohol (2-BuOH), ethane-1,2-diol (EG), propane-1,2-diol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) was studied at several temperatures and a fixed atmospheric pressure. The equilibrium approach was used to measure the solubility of ITN, and the Apelblat, van't Hoff, and Buchowski−Ksiazczak λh models were used to correlate the results. The overall uncertainties were less than 5.0% for all the models examined. The highest ITN mole fraction solubility was achieved as 1.01 × 10−1 in DMSO at 318.2 K; however, the least was achieved as 3.16 × 10−7 in water at 298.2 K. ITN solubility was found to be enhanced with an increase in temperature and the order in which it was soluble in several green solvents at 318.2 K was as follows: DMSO (1.01 × 10−1) > EA (1.73 × 10−2) > PEG-400 (1.66 × 10−2) > THP (1.59 × 10−2) > 2-BuOH (6.32 × 10−3) > 1-BuOH (5.88 × 10−3) > PG (4.83 × 10−3) > EtOH (3.51 × 10−3) > EG (3.49 × 10−3) > MeOH (2.10 × 10−3) > water (1.38 × 10−6). ITN−DMSO showed the strongest solute−solvent interactions when compared to the other ITN and green solvent combinations. According to thermodynamic studies, ITN dissolution was endothermic and entropy-driven in all of the green solvents tested. The obtained outcomes suggested that DMSO appears to be the best green solvent for ITN solubilization.

Prevalence, knowledge and attitude toward electronic cigarette use among male health colleges students in Saudi Arabia-A cross-sectional study.

Background: Health care professionals have an important role in increasing awareness about smoking harms and serving as role models. This study aims to assess knowledge, attitude and perception toward electronic cigarettes (ECs) as well as prevalence of ECs use among male health colleges students. Method: This is a cross-sectional survey-based study conducted among students in the male campus of five different health colleges over a 4-month period from February 2020 to May 2020. Descriptive analysis was used to assess the knowledge, perception and attitude, and inferential testing was used to evaluate the association of different participant's variables and knowledge toward ECs usage using SPSS. Results: A total of 333 students were included in the analysis. Most of students (n = 205; 61.6%) had never used ECs, while 22.8 and 15.6% used them for recreational and smoking cessation purposes, respectively. Focusing on ECs users from each college individually, medical students had the highest prevalence followed by dental, pharmacy and nursing students (47.4, 40.7, 34.5, and 32%, respectively). Many students had misconceptions and a low level of knowledge about ECs, such as recognizing them as smoking-cessation tools and not knowing whether toxic and carcinogenic components levels in ECs are similar to conventional cigarettes, respectively. Medical students had significantly higher knowledge compared to dental students [3 (2) vs. 2 (1); p = 0.033]. Moreover, smokers were less knowledgeable than non-smokers [2.5 (1) vs. 2.1 (1), p = 0.027]. At least 62.8% of students perceived using ECs as a fashionable alternative smoking method and 59.2% believed that they may become a gateway for smoking addiction. Only 120 (36.0%) health colleges students were confidently able to advise smokers regarding ECs. Conclusion: Our study highlights an increased trend of ECs use accompanied with insufficient knowledge and several misconceptions about ECs among health colleges students. This was associated with a negative influence on their attitude toward ECs use, which would potentially lead to negative consequences on public health.

Does Ramadan fasting disrupt international normalised ratio control in warfarin-treated medically stable patients?

AIM: Warfarin is commonly used in patients with thrombotic diseases. This study aimed to evaluate the impact of Ramadan fasting on warfarin efficacy by investigating international normalised ratio (INR) stability in medically stable patients. METHODS: A retrospective observational study was conducted at King Khalid University Hospital during Ramadan 2016 on fasting adult patients aged above 18 years and receiving warfarin. The INR values during pre-Ramadan, Ramadan and post-Ramadan periods were collected after satisfying the inclusion criteria. Time within the therapeutic range (TTR) during the whole period was estimated using the conventional method. RESULTS: In total, 101 patients were included in the study. The mean age (SD) was 55.8 ± 15.5 years, and 52.4% were females. The target INR range for 62.4% was 2-3, while 37.6% had a target INR range of 2.5-3.5. An upward trend in the proportion of patients with therapeutic INR was noticed during Ramadan (59.4%) as compared to pre- (56.4%) and post-Ramadan periods (53.5%) respectively. Additionally, the proportions of patients with supratherapeutic and sub-therapeutic INR were the highest and lowest, 23% and 24% respectively post-Ramadan as compared to other periods. Based on target INR categorisation, achieving therapeutic INR during Ramadan was more feasible with the low INR (2-3) compared to the high INR (2.5-3.5) target patients, 63.5% vs 52.6% respectively. TTR estimation revealed 62.4% and 37.6% of the patients had good and poor, respectively, anticoagulation status throughout the study period. CONCLUSION: Despite the changes in mean INR and proportion of patients with therapeutic INR during Ramadan compared to other non-fasting months, our results confirmed that short-term fasting during Ramadan has no significant influence on INR stability and, consequently, therapeutic efficacy in warfarin-treated medically stable patients.