New Approach for Administration of Doxazosin Mesylate: Comparative Study between Liquid and Solid Self-nanoemulsifying Drug Delivery Systems

Self-nanoemulsifying drug delivery systems (SNEDDS) in both liquid and solid forms were suggested to improve water solubility of Doxazosin mesylate (DOX) a poorly water- soluble antihypertensive drug. Oleic acid: Smix (1:9 w/w) and Tween 80: co-surfactant mixture (Ethanol and PEG 400) (1:1, 2:1, 3:1 and 4:1) were chosen to prepare a liquid and solid forms of SNEDDS according to their solubility. TEM images revealed change in the crystalline nature of DOX into uniform particles with smooth surface. Characterization studies revealed droplet size ranges from 79.80±14.39 to 273.10±4.17 nm, zeta potential ranges from -5.57±0.10 to -21.13±0.46 mV and dissolution enhancement of more than two folds with more favorable properties for the solid forms. FTIR demonstrated significant physical changes in DOX crystalline structure. In conclusion, the solid SNEDDS containing oleic acid: Smix (1:9 w/w) and Tween 80: co-surfactant mixture (3:1 w/w) and adsorbent mixture of Avicel 101 and Aerosil 200 (40:1 w/w) might be a promising formula for better management of hypertension with expected shelf stability.

Improved Hypertension by Investigating Circadian Rhythm of Blood Pressure

Case: The case is 86-year-old male hypertensive patient with anti-hypertensive drug for 5 years. He has been provided Amlodipine besilate 5mg at 0800h and doxazosin mesylate 2mg at 2300h for long. In June 2020, he noticed unstable fluctuation of Blood Pressure (BP) during morning, afternoon and night. Results: Then, he checked the circadian rhythm of BP, which showed higher BP in early morning, decreasing BP 0800-1000h, minimum BP during 1000-1400h, increasing BP during 1400-1800h and stable BP during 1800-2400h. Due to the result, he changed to take amlodipine at 2300h. Consequently, his BP gradually became stable during 24 hours after 2 weeks. Discussion: Some factors may exist for contributing improved BP fluctuation. They include a) pathophysiological characteristics of BP circadian rhythm, b) effective time for anti-hypertensive drug, c) accuracy of the obtained BP data and d) the social and psychological reliability of the patient. Regarding d) he was engaged in research and development work as a senior researcher at a chemical company. He has been also a member of New Elderly Association (NEA), which was established by Shigeaki Hinohara. He lives on the philosophy of Hinohara-ism for long, associated with stable mind and body.

Linear pharmacokinetics of doxazosin in healthy subjects

Doxazosin is used for treating symptoms of benign prostatic hyperplasia (BPH). Besides, it is also prescribed for patients with mild to moderate essential hypertension. The object of the current study was to assess the linearity in the pharmacokinetics of doxazosin after administration of doxazosin as a single dose tablet containing 2, 4 and 8 mg doxazosin mesylate. Thirty Iraqi healthy male adult subjects were given 2, 4 and 8 mg doxazosin mesylate tablet in a randomized, cross-over, open-label, fasting, three-period, three-sequence design separated by one week wash out the interval between dosing. Serial blood samples were obtained from each subject before drug intake (zero time) and then at 0.33, 0.67, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36, 48, 60, and eventually at 72 hours after dosing. The pharmacokinetic parameters Cmax, AUC0–t, AUC0–∞, Tmax and Thalf were determined from plasma concentration-time data of the drug by non-compartmental analysis. Statistical analysis of doxazosin pharmacokinetic parameters obtained after administration of the investigated dose ranges 2-8 mg demonstrated linear pharmacokinetics.