First Report of Erythema Multiforme Minor Caused by Raloxifene Hydrochloride

Raloxifene is a drug used in postmenopausal women with osteoporosis. Although hot flashes are known side effects of raloxifene, to the best of our knowledge, erythema multiforme (EM) minor has not been previously reported. Herein, we report about a 74-year-old woman who developed EM minor after the drug alfacalcidol was changed to raloxifene to treat osteoporosis. Skin biopsy revealed a suspicious eczematous drug reaction. The drug-induced lymphocyte stimulation test showed a positive result. The stimulation index was 2.2, and there were no other suspected drugs. Based on these results, we diagnosed the condition as EM minor caused by raloxifene. The patient’s symptoms disappeared after the use of antihistamine drugs and topical steroids. In conclusion, raloxifene can cause EM minor in rare cases.

Formulation and Evaluation of Self Nano Emulsifying Drug Delivery System of Raloxifene Hydrochloride

Raloxifene hydrochloride (RLX) is a selective Estrogen-receptor modulator used to treat osteoporosis as well as breast and endometrial cancer prevention. The bioavailability of RLX is only 2% due to substantial pre-systemic clearance. The goal of this research was to customise and characterise RLX-loaded self-nanoemulsifying drug-delivery systems (SNEDDS) by using bioactive excipients that impact drug metabolism. The droplet size, zeta potential and drug content determination of optimized formulation (F-06) was found to be 147.5 nm, -28.8, 99.67% respectively. The drug release study from the nano formulation was studied in Phosphate buffer 6.8 for all the formulations F1,F2,F3,F4,F5,F6 and F7. The optimized formulation was found to be F6 Keywords: Raloxifene hydrochloride, nanoemulsion, SNEDDS

Formulation and evaluation of raloxifene hydrochloride dry emulsion tablet using solid carrier adsorption technique

Aim: The present study focused on the development of a dry emulsion tablet of raloxifene hydrochloride (RXF) using a solid carrier adsorption technique to enhance oral bioavailability. Methods: An oil-in-water emulsion was formulated and converted into dry powder using HPMC K4M plus Aerosil 200, then compressed into tablets. Results: The prepared emulsion was evaluated for globule size, drug content and zeta potential. In vitro release study revealed significantly higher release from emulsion. The prepared tablets possessed acceptable hardness, friability, weight variation, disintegration time, thickness, etc. In vivo pharmacokinetic studies indicated a more than sevenfold increase in oral bioavailability. Stability studies indicated good physical and chemical stability of the developed formulation. Conclusion: The authors successfully formulated dry emulsion tablets with enhanced oral bioavailability.

Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment

Raloxifene hydrochloride (RLX), an antiosteoporotic agent, has been utilized for guarding against breast cancer and recently, for the disease management owing to its estrogen antagonist activity. Nevertheless, RLX exhibits poor bioavailability that could be attributed to reduced water solubility and first pass metabolism. To overcome these challenges, this study aimed at formulating and optimizing RLX emulsomes (RLX-EMLs) to enhance the drug antitumor activity. A 4131 factorial design was employed for assessing the effect of lipoid: solid lipid ratio and solid lipid type on the emulsomes characteristics. The anticancer potential of the optimized formulation and apoptotic parameters were assessed. Vesicle size, entrapment, and release efficiency were significantly influenced by both variables, while zeta potential was influenced by lipoid: solid lipid at p < 0.05. The optimal formulation exhibited vesicle size of 236 ± 8.6 nm, zeta potential of −18.6 ± 0.7 mV, drug entrapment of 98.9 ± 4.9%, and release efficiency of 42.7 ± 1.8%. MTT assay showed concentration-dependent inhibition of MCF-7 cells viability. In addition, cells treated with RLX-EMLs showed significant arrest at G2/M phase associated with significant increase in apoptotic and necrotic cells. The enhanced cytotoxic and anti-proliferative effect of RLX-EMLs relative to raw drug was authenticated through increased Bax/Bcl-2 ratio, caspase-9 activation and depletion of mitochondrial membrane potential.

DEVELOPMENT AND EVALUATION OF MEDICATED CHEWING GUM OF RALOXIFENE HYDROCHLORIDE

In this study we formulate Raloxifene hydrochloride, edicated chewing gum to overcome first pass metabolism of it so bioavability increase of drug. We take polyvinyl acetate as chewing gum base. Aspartame, mannitol and sucrose as sweetener. Glycerin as a plasticizer. Beta-cyclodextrine as solubility enhancer and taste masking agent. First we evaluate the API by its melting point after we derived its calibration curve. After this we select proper ratio of Beta-cyclodextrine and API. After we study drug and excipients compatibility by using FTIR. XRD study perform for API and formulation. After we formulate our formulation and perform post-evaluation study like hardness, weight variation, % drug content and % drug release. From all formulation F5 formulation shows best % drug release and % drug content. After we perform stability study for our formulation and after study no major change show in formulation. And in last we perform buccal permeability study. On basis of all study results we can say that our formulation is successfully formed. Keywords: Raloxifene hydrochloride, Medicated chewing gum, Buccal permeation, Osteoporosis.

IN SILICO IDENTIFICATION OF APOBEC3B SMALL MOLECULE INHIBITORS FROM DTP-NCI LIBRARIES

Objective: APOBEC3B (A3B) enzyme causes C-to-T or C-to-G somatic alteration in the cancer genome, leading to the evolution of a broad spectrum of human cancers. The present study aims to identify A3B small molecule inhibitors using a top-down approach via pharmacoinformatic virtual screening. Methods: Virtual screening of 2951 drug-alike molecules with diversified structures from the National Cancer Institute Development Therapeutics Program (DTP-NCI) compounds library was performed using GOLD and AutoDock Vina docking programs against the 3D structure of A3B (PDB ID: 5TD5). Results: Amongst the docked compounds, Nordracorubin, NSC641233 and Raloxifene hydrochloride showed the most potent binding affinities towards A3B on both Autodock/Vina and GOLD. Several significant similarities were observed between A3B and the three hits, including hydrogen bonds and pi-pi stacking. The three compounds also exhibited interaction with the centralized zinc cofactor and amino acid residues that directly contribute the deaminase activity of A3B enzyme. Conclusion: We hypothesize that the findings from this study could significantly shorten the quest for novel molecules against the A3B after confirmation with subsequent in vitro and in vivo studies in the near future.