Formulation And Evaluation of Fast Dissolving Oral Films Incorporated With Ramipril and β-Cyclodextrin Complex

Abstract Ramipril being ACE inhibitor belongs to BCS class II drug with low solubility and undergoes first-pass metabolism that leads to reduced bioavailability of 28%. The current research is aimed at formulating and evaluating ramipril fast dissolving oral films (FDOF). Solubility enhancement of ramipril was done by formation of inclusion complex with β-cyclodextrin in 3 ratios (1:0.5, 1:1, 1:2). Based on higher drug content and dissolution values the physical mixture of ramipril with β-cyclodextrin in 1:1 ratio (IC2) was chosen for further studies. Total 12 formulations of ramipril FDOF containing IC2 prepared with various polymers and evaluated for physicochemical properties. The optimized formulation F9 shown better tensile strength (11.6 g/cm2), significant % elongation (9.8) and maximum % drug content of 99.98 %. The formulation F9 exhibited minimum disintegration time of 9 sec that is desirable for immediate onset of action and maximum drug release. The FTIR data of F9 assured the compatibility of drug and formulation excipients, found to be stable for 180 days at accelerated conditions. The study confirmed that ramipril FDOF lead to quicker onset of action and enhanced therapeutic efficiency in comparison to marketed product.

A network meta-analysis on the influence of antihypertensive agents on new-onset diabetes / 中国药学杂志

OBJECTIVE: To comprehensively evaluate the influence of antihypertensive agents on new-onset diabetes, including diuretics, beta-antagonists, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and calcium channel blockers (CCB). METHODS: Clinical trials were searched about antihypertensive agents and NOD. The ORs and rankings of the five classes of drugs and placebo were estimated, using random effects Bayesian models in WinBUGS version 1.4.3. RESULTS: Twenty-eight clinical trials were included in this study. Compared to placebo, the ORs of the five classes of drugs for causing NOD were as follows: ARB 1.23(95%CI:1.087-1.399), ACEI 1.204(95%CI:1.033-1.424), CCB 0.9289(95%CI:0.7793-1.095), beta-antagonists 0.7384(95%CI:0.6047-0.8906), diuretics 0.7894(95%CI:0.654~0.9283). CONCLUSION: The probability of causing NOD is lowest for ARB followed by ACEI, placebo, CCB, diuretics and beta-antagonists. ARB and ACEI can reduce the risk of NOD. CCB, diuretics and beta-antagonists can increase the risk of NOD.

Analysis of Treatment Patterns and Blood Pressure Changes According to Risk Stratification in Hypertensive Subjects / 대한내과학회지

BACKGROUND/AIMS: The aims of this study were to identify real world treatment patterns of hypertension according to cardiovascular risk stratification and to evaluate blood pressure changes with anti-hypertensive treatment in each risk group. METHODS: This study included patients who were newly-diagnosed with hypertension or known hypertensive patients with uncontrolled blood pressure (BP) at seven tertiary hospitals in Busan and Ulsan. World Health Organization/International Society of Hypertension (WHO/ISH) cardiovascular risk stratification was performed through retrospective chart review. RESULTS: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were the most frequently prescribed drugs. The higher WHO/ISH risk group received a greater number of drugs at the initial treatment, and one year after treatment. Target BP was achieved less frequently in the higher risk group (68.2% vs. 85.2% vs. 89.0%, p < 0.001). The rate of attaining target BP was lower (50.7% vs. 81.6%, p < 0.001), and the time to attaining target BP was longer (106.5 +/- 79.2 days vs. 82.1 +/- 75.3, p = 0.001), in patients with renal disease or diabetes. Initial systolic BP above 160 mmHg (OR: 4.91, 95% CI: 2.27~10.65), renal disease (3.42, 1.60~7.32), medium or high risk group status (2.27, 1.23~4.20), initial diastolic BP above 100 mmHg (2.11, 1.11~4.04), and diabetes (2.06, 1.29~3.25) were independent factors that predicted failure of attaining the target BP. CONCLUSIONS: BP control was relatively unsatisfactory in patients with higher initial BP, renal disease, higher WHO/ISH risk group status, and diabetes. Individualized approaches for such patients are needed to improve BP control in routine clinical practice.

Use of antihypertensive drugs among community hypertensive patients in Shanghai / 中华全科医师杂志

Objective To investigate use of oral antihypertensive drugs among community hypertensive patients in Shanghai and find out factors related to their unreasonable use to direct their clinical use. Methods Seven hundred and three hypertensive patients were surveyed with questionnaire by stratified cluster sampling at three neighborhoods and one village of Dahua community, Baoshan district, Shanghai during April to June 2009 to understand their use of antihypertensive agents, including kinds and forms of drugs, rationale of drug use. Results Five hundred and eighty-two (82. 8% ) of 703 hypertensive patients interviewed were using antihypertensive drugs, 271 (38. 5% ) of them used only one kind of non-compound antihypertensive drug, 182 (25.9%) used one kind of compound agent, 311 (53.4%) used two or more kinds of drugs in combination, including 117 patients ( 16. 8% ) used two kinds of agents combined and 12 patients ( 1.6% ) used three kinds of agents combined. Two hundred and sixty-six (47.5%) patients took orally calcium-channel blockers and 205 ( 35.2% ) used compound agents. Conclusions Frequency of combined use of two or more kinds of antihypertensive agents is reasonable and significantly higher than that of use of one kind of drug at Dahua community in Shanghai. Calcium channel blocker plays a predominant role in treatment for hypertension, non-long-acting compound agents are used in a higher proportion. But,guidelines for hypertension prevention and treatment are not so well complied with in local hypertensive patients. So, it is suggested that training for community physicians and management for standard use of antihypertensive agents at community should be strengthened further.

Long-term Effect of Different Antihypertensive Agents on Renal Hemodynamics / 中国康复理论与实践

@#ObjectiveTo investigate the long term effect of different antihypertensive agents on renal hemodynamics with ultrasound Doppler.Methods52 essential hypertensive patients were divided into three groups according to the antihypertensive agent they took: angiotensin-converting-enzyme inhibitor (ACEI), calcium channel blocker (CCB) and β-adrenoceptor blocker (βB). The blood pressures of right upper arms were measured with mercury column blood pressure gauge using Korotkoff method. Renal hemodynamics were examined with ultrasound Doppler before and after treatment with agents. ResultsSystolic blood pressure (SBP) and diastolic blood pressure (DBP) of all patients were decreased significantly. An significant correlation was found between the deceases of blood pressure and the betterment of renal homodynamic parameters in ACEI and CCB groups, but not in βB group. ConclusionTo a degree, the betterment of renal hemodynamics is correlation with the reduction of systemic blood pressure and mechanism of action of antihypertensive agents.

On the Utilization of Antihypertensive and Antibacterial Agents / 薬剤疫学

Here we report the results of a long-term analytical study on the utilization of antihypertensive and antibacterial agents, which was performed using the Integrated Medical Information System (IMIS) developed by Kochi Medical School. The results indicate clear (increasing or decreasing) patterns in the numbers of patients and the dosages. Specifically, the total amount of antibacterials recently prescribed is significantly lower than in the year analysis began (1983). This reduction provides evidence of a steady improvement in the quality of medication and is particularly important for macrocosmic evaluation of the primary focus of our study, which was the “proper use of drugs”. Furthermore, the results also showed medication prescribed by non-specialists to be less inventive than that prescribed by specialists. This study highlights the importance of reforming institutions providing medical treatment from the perspective of effectively utilizing medical resources (by employing specialist personnel) and the proper use of medications. Because non-specialists prescribe medication in numerous medical facilities throughout Japan, these issues must be seriously considered.

A prospective study on the antihypertensive monotherapy in family practice

BACKGROUND: There are very few cohort studies on the hypertension in family practice. In order to investigate epidemiological characteristics of hypertensive patients and assess the safety and tolerability of newly prescribed antihypertensive monotherapies in Korean patients, a prospective study was carried out. METHODS: A total of 1,181 patients were observed from July 1997 to August 1999. At 2, 4, 8 and 12 weeks after initiation of antihypertensive monotherapy, the patients were evaluated for whether treatment is continued and development of any adverse reactions. RESULTS: Calcium channel blockers(CCBs) were the most commonly prescribed initial drug class (44.2%) in family practice, followed by angiotensin converting enzyme inhibitors(ACEI)(21.0%), angiotensin II receptor antagonists(ARA)(11.8%), beta blockers(9.6%), alpa blockers(3.9%), and diuretics(3.6%). During the first 12 weeks, the percentage of subjects continuing their initial ACEIs(40.7%) was substantially lower than the percentages that of subjects continuing ARAs(66.2%), alpa blockers(63.0%), CCBs(61.3%), beta blockers(55.8%), and diuretics(53.5%), respectively(P<0.01). The following adverse reactions were detected: cough(7.5%), headache(6.1%), dizziness(3.9%), flushing(3.7%) and impotence(2.4%). The incidence of cough associated with ACEI(27.9%) was higher than those of other classes(P<0.01). CONCLUSION: CCBs were the most commonly prescribed initial drug class in family practice, followed by ACEIs, ARAs, beta blockers, alpa blockers, and diuretics. The tolerability of antihypertensive medication was the highest in Korean patients treated with ARAs, followed by CCBs, beta blockers, diuretics, alpa blockers, and ACEIs.

The Clinical Effects of Perindopril(Acertil(R)) on Hypertensive Patients

BACKGROUND: Perindopril. a new second-generation angiotensin converting enzyme inhibitor developed by Servier Research, was administered in essential hypertensive patients in order to observe the clinical effects. METHOD: The changes of blood pressure, heart rate, quality of life, clinical laboratory examinations, side effects, electrocardiogram and echocardiographic left ventricular mass were evaluated before and after 4-12mg of perindopril 12 weeks' administration in 25 essential hypertensive patients(mild 10, moderate 8, severe 5, very severe 2 : male 7, female 18 ; mean age 53.1+/-8.9 years). RESULT: 1) After treatment with perindopril alone, blood pressures were lowered markedly in 17(68%), moderately in 5(20%) and mildly in 2(8%) cases. The average of blood pressures of 25 subjects were systolic 173.1+/-22.8mmHg and diastolic 105.9+/-9.5mmHg before treatment, which were lowered to 125.2+/-14.9mmHg and 83.2+/-9.0mmHg respectively after 12 weeks(p<0.0001). 2) Quality of Life improved markedly in 11(44%) and slightly in 9(36%) cases after perindopril administration. 3) On electrocardiographic follow-up study, three out of five left ventricular hypertrophy with strain, seven out of 13 left ventricular hypertrophy, two out of three ST segment and T wave change and two sinus tachycardia were improved. Echocardiographic left ventricular mass was reduced significantly form 249.4+/-72.7g to 202.9 56.3g after 12 weeks perindopril treatment(p<0.0001). 4) Side effects were 5 cases of dry cough and 3 facial flushing. 5) Final Assessment of perindopril effect including hypotensive effect, quality of life, left ventricular mass regression and side effect showed very useful in 16(64%) and useful in 6(24%) out of 25 subjects. CONCLUSION: Perindopril may be an effective initial single antihypertensive agent for the treatment of varying degree of hypertension, especially with left ventricular hypertrophy.