Impact of crystal polymorphism of rifaximin on dissolution behavior.

Introduction: Rifaximin is an intestinal antiseptic which has five (pseudo) polymorphs α, ß, γ, δ and ε. These last (pseudo)polymorphs have different physicochemical properties. The objective of the study is to assess the impact of rifaximin polymorphism on its dissolution rate which could affect its bioavailability. Material and methods: The analytical validation of dissolution assay method by UV-Visible spectrophotometry was carried out according to ICH Q2. The physicochemical characterization (solubility test, FTIR, DSC, XRD) was carried out on four active pharmaceutical ingredient (MP1, MP2, MP3, MP4). MP1 and MP2 were used by the manufacturer of generic brand 1 (G1) and MP3 and MP4 were used by the manufacturer of generic brand 2 (G2). The comparative in-vitro dissolution study was carried out on the leader brand (P), G1 and G2. Results: The four MPs were analyzed by XRD. The results of analysis showed that MP1 and MP4 were a mixture of α form and amorphous form. MP2 had an amorphous form and MP3 had a crystalline form ß. The spectra of FTIR showed that the four MP had characteristics bands of rifaximin in the domain 4000-400 cm-1. The differences between the spectra of the four MPs were observed among the amorphous form (MP2), around the region 1800 to 1820 cm-1 which is attributed to the vibration of the CO group. An additional difference observed among the amorphous form (MP2) is around the region 1400 cm-1 which is attributed to the banding OH. The thermograms of MP1, MP2 and MP4 showed endothermic peaks which are probably attributed to the departure of water which indicate that MP1, MP2 and MP4 are pseudopolymoph (hydrate). For the four MPs, probably the melting points are interrupted by the phenomenon of phase transformations (Crystallization) which are reflected by exothermic peaks around 200°C-250 °C.Our results showed that the crystalline polymorphism of rifaximin influences its solubility. According to the results of the solubility test, the ß crystal form of rifaximin (MP3) had the lowest solubility (3.47 µg/ml). MP2 had the highest solubility (8.35 µg/ml) and MP1 and MP4 had intermediate solubilities (5.47 µg/ml and 6.74 µg/ml). Comparative in vitro dissolution results showed that the dissolution profile of P was not similar to that of G1 and G2 (% dissolution (P)30min = 60%; % dissolution (G1) 30 min = 100% and % dissolution (G2) 30 min = 115%; f1(P versus G1) = 44; f1(P versus G2) = 61) in M1, while G1 and G2 had comparatively similar dissolution profiles (% dissolution (G1) 30 min = 100%; % dissolution (G1) 30 min = 110%; f1 (G1 versus G2) = 14) in M1. Conclusion: This study highlighted the impact of rifaximin polymorphism on its physico-chemical properties (crystal structure, thermal behavior, solubility) and on its dissolution behavior which could affect the rifaximin bioavailability.

Prevalence and risk factors of trastuzumab induced cardiotoxicity in Tunisian HER2-positive breast cancer patients.

INTRODUCTION: Cardiotoxicity is the most important side effect of Trastuzumab treatment. The purpose of this study is to evaluate the prevalence of Trastuzumab induced cardiotoxicity and to analyze risk factors associated with this side effect. MATERIALS AND METHODS: A retrospective institutional study was carried out from June 2018 to December 2018 at the department of Medical Oncology of Salah Azaiz institute, Tunis, Tunisia. Demographic, clinical characteristics (menopausal status, breast cancer stage, anthracyclines exposure, comorbidities presence…) and left ventricular ejection function (LVEF) measurements, were collected from patient records. RESULTS: Twenty-three women (20%) had Trastuzumab induced cardiotoxicity.65.2% (N = 15) experienced a decrease in LVEF more than 10% with a decrease below normal value and 34.8% (N = 8) experienced a decrease in LVEF more than 20%. Obesity is a risk factor for the occurrence of Trastuzumab induced cardiotoxicity (adjusted odds ratio (OR) = 2.919 (95% confidence interval (CI) [1.0411-8.186]; p = 0.042). CONCLUSION: Our study highlighted that obesity is associated with a high risk of cardiotoxicity in women treated with Trastuzumab. Therefore, close monitoring of cardiac function is recommended especially for obese women during Trastuzumab administering.

Patterns of complementary and alternative medicine use among Tunisian cancer patients.

INTRODUCTION: The use of complementary and alternative medicine (CAM) among cancer patients is prevalent worldwide as cancer patient are perpetually seeking for a way to improve their quality of life and to cure their disease. Unfortunately, the majority ignore the danger that can resort when they use CAM currently with conventional therapies. The purpose of this study is to assess prevalence and predictors of CAM use in cancer patients. METHODS: Cross-sectional study using a questionnaire administered to cancer patients, who were attending Salah Azaiz institute, Tunis, Tunisia. The study took place from September to December 2018. RESULTS: In 222 cancer patients, the overall prevalence of CAM use was 40.54%. On univariate analysis, patients who had university education level were less likely to use CAM (p = 0.05). Based on multivariate analysis, CAM users had more likely metastatic tumor (p = 0.047; OR = 1.913).It is reported that the majority of the population used herbal medicine. The most common herbal products consuming by patients, included Ephedra foeminea (51.8%), Annona muricata (12%) and Curcuma longa L. (10.84%).The main source of information was entourage (family, friends, hospital entourage) (74.44%).The majority of CAM users (61.11%) reported to consume CAM currently with conventional therapies. CONCLUSION: This survey revealed a high prevalence of CAM use. The most common type of CAM use is herbal products. Some of the used herbal products are known to interact with conventional anticancer medication. This emphasizes the importance of patients disclosure of CAM use to health professionals in order to avoid herb-medications interactions.

Toxicity, risk factors and management of cisplatin-induced toxicity: A prospective study.

BACKGROUND AND PROPOSE: Cisplatin is a cytotoxic drug that triggers several toxicities. However, nephrotoxicity and ototoxicity remain major clinical limitations. The aim of our study was to evaluate the incidence of chemotherapy toxicity induced by cisplatin and to analyze the influence of risk factors in the Tunisian population. METHODS: We performed a prospective descriptive study in a period of four months. Patients were eligible if they had pathologically confirmed malignancies and treated with cisplatin-regimen chemotherapy. Nephrotoxicity and digestive toxicity were graded according to the World Health Organization toxicity scale and ototoxicity was scored clinically according to the Common Terminology Criteria for Adverse Events (CTCAE). Multivariate logistic regression analysis was performed to evaluate the influence of clinical variables on cisplatin-induced toxicity. RESULTS: A total of 150 patients were included. Forty-four percent of patients developed cisplatin-regimen toxicity: 15% developed cisplatin-induced nephrotoxicity, 9% cisplatin-induced ototoxicity and 27% digestive toxicity. In the multivariate analysis, age >65 years (OR= 6.129, p = 0.010), metastatic cancer (OR = 0.171, p = 0.007) and cumulative dose (OR= 1.004 mg/m2; p = 0.042) were strong predisposing factors for CDDP-induced nephrotoxicity. The cumulative dose was an independent prognostic indicator for digestive toxicity (OR = 0.997, p = 0.002). CONCLUSION: In our study, age >65 years and metastatic cancer were risk factors for cisplatin-induced nephrotoxicities. We also found the correlation between cumulative dose and nephrotoxicity or digestive toxicity.