Controlled Release Diltiazem Research Articles

A Five-Year Stability Study of Controlled-Release Diltiazem Hydrochloride Tablets Based on Poly(Ethylene Oxide)

Effects of Rosiglitazone and Acarbose (with and without Cornstarch Diet) on Serum Electrolytes in Diabetic RatsHumera Khatoonand Rahila Najam

Rhabdomyolysis Caused by a Potential Sitagliptin‐Lovastatin Interaction

A 75-year-old woman with diabetes mellitus, hypertension, and hyperlipidemia came to the emergency department with generalized and upper-extremity weakness; she had experienced a fall 2 months earlier. On admission, her drug therapy included lovastatin 40 mg/day, controlled-release diltiazem 240 mg/day, and glimepiride 1 mg/day. Nineteen days earlier, sitagliptin 100 mg/day had been started; it was discontinued 2 weeks later, and glimepiride was begun. A cardiology consultation performed on the day of admission determined that a markedly elevated creatine kinase-myocardial band isoenzyme level and borderline-high troponin I level were diagnostic of rhabdomyolysis secondary to statin use. Because the patient had been taking lovastatin for the past 12 years, the possibility that the rhabdomyolysis may have been caused by a drug interaction between lovastatin and a concomitant drug was evaluated. As it had been 10 months since her last dosage adjustment of diltiazem, it was unlikely that the statin-induced rhabdomyolysis was precipitated by diltiazem. Use of the Drug Interaction Probability Scale to determine the strength of a lovastatin-sitagliptin interaction indicated a possible association (score of 4). Multiple drug interactions have been reported with lovastatin. To our knowledge, however, this is the first case report of a possible sitagliptin-lovastatin interaction that may have caused rhabdomyolysis. Studies must be performed to further evaluate the in vivo effect of sitagliptin on the cytochrome P450 3A4 enzyme system and to elucidate other mechanisms that may potentiate such a drug-drug interaction. In the meantime, however, clinicians should be aware of this possible drug interaction.

Development and release mechanism of diltiazem HCl prolonged release matrix tablets

A coated matrix tablet formulation has been used to develop controlled release diltiazem HCl (DIL) tablets. The developed drug delivery system provided prolonged drug release rates over a defined period of time. DIL tablets prepared using dry mixing and direct compression and the core consisted of hydrophilic and hydrophobic polymers such as hydroxypropylmethylcellulose (HPMC), Eudragits RLPO/RSPO, microcrystalline cellulose, and lactose. Tablets were coated with Eudragit NE 30D, and the influence of varying the inert hydrophobic polymers and the amount of the coating polymer were investigated. The release profile of the developed formulation was described by the Higuchi model. Stability trials up to 6 months displayed excellent reproducibility.

Warfarin and Royal Jelly Interaction

An 87-year-old African-American man came to the internal medicine clinic for a routine anticoagulation management visit. He had no complaints. His medical history was significant for stage IV-A follicular non-Hodgkin's lymphoma, atrial fibrillation, and hypertension. His long-term drug therapy consisted of warfarin, felodopine, lisinopril-hydrochlorothiazide, controlled-release diltiazem, potassium chloride, and oxycodone. He reported adherence with his prescribed drugs and denied taking any over-the-counter or herbal products. Overall, the patient's drug therapy had been consistent during the preceding 3 months, no significant changes had occurred in his clinical status, and no significant changes had been noted in his diet; his international normalized ratio (INR) had ranged from 1.9-2.4 (therapeutic range 2-3). He denied tobacco use, alcohol consumption, and recent travel. Four weeks later, the patient came to the emergency department with hematuria. He denied dysuria, taking more than the prescribed amount of warfarin, any changes in his diet, taking any over-the-counter or herbal products, and any other bleeding. On admission to the hospital, his INR was 6.88, which increased to 7.29 during his hospital stay. On further investigation, the patient admitted that he had started taking an herbal supplement, royal jelly, 1 week earlier. When asked specifically about the ingredients in the supplement, he stated that royal jelly was the only component. Relative to the patient's denial of any other changes in his condition or drug regimen, the most probable explanation for his elevated INR and subsequent bleeding is a possible interaction between royal jelly and warfarin. To our knowledge, no case reports concerning royal jelly and warfarin taken concomitantly have been reported. Clinicians should be proactive and repeatedly provide education regarding the potential dangers of dietary supplements taken with conventional drugs.

Gastrointestinal Transit Monitoring and Absorption of Controlled-Release Pellets of Diltiazem

The gastrointestinal (GI) transit and absorption of a multiparticulate controlled-release diltiazem formulation were investigated with reference to an innovator preparation. Transit of controlled-release pellets in GI tract was monitored using two marker drugs, namely paracetamol and sulfasalazine. Both formulations had little intersubject variation in gastric emptying and small intestine transit time. In both formulations, about 51% to 64% of the drug was absorbed while pellets were in the small intestine and the remaining amount while in the colon. The results found in this study were comparable to the other workers who used gamma scintigraphy or indirect method. Therefore, the method used in this study is a reliable alternative for studying GI transit of pellets.

Application of Similarity Factor in Development of Controlled-Release Diltiazem Tablet

Controlled-release grade hydroxypropylmethylcellulose (HPMC) or xanthan gum (XG) and microcrystalline cellulose (MCC) were employed to prepare controlled-release diltiazem hydrochloride tablets. The similarity factor f2 was used for dissolution profile comparison using Herbesser 90 SR as a reference product. Drug release could be sustained in a predictable manner by modifying the content of HPMC or XG. Moreover, the drug release profiles of tablets prepared using these matrix materials were not affected by pH and agitation rate. The f2 values showed that only one batch of tablets (of diltiazem HCl, HPMC or XG, and MCC in proportions of 3.0:3.0:4.0) was considered similar to that of the reference product, with values above 50. The unbiased similarity factor f*2 values were not much different from the f2 values, ascribing to a small dissolution variance of the test and reference products. The amount of HPMC or XG incorporated to produce tablets with the desired dissolution profile could be determined from the curves of f2 versus polymer content. Hence, the f2 values can be applied as screening and optimization tools during development of controlled-release preparations.

Comparison of nisoldipine coat-core and diltiazem controlled-release tablets in the treatment of chronic stable angina in elderly patients: A multicenter study

Abstract The purpose of this randomized, double-blind, double-dummy, 12-week trial was to compare the efficacy and tolerability of nisoldipine coat-core (CC), a new extended-release formulation, with those of diltiazem controlled-release (CR) tablets. These 2 oncedaily calcium channel blockers were compared as second-line treatment of chronic stable angina in elderly patients who were receiving concurrent beta blocker and nitroglycerin therapy. The primary end point was time to electrocardiogram or symptom-related termination of exercise on treadmill testing at trough drug levels. Two hundred ninety-three patients 60 to 80 years of age with New York Heart Association Class II or III chronic stable angina pectoris of ≥3 months' duration were recruited from 23 hospital centers in the United Kingdom. After a 2-week placebo run-in period, patients who terminated exercise within 2 to 9 minutes on treadmill testing were allocated randomly to receive nisoldipine CC 10 mg or diltiazem CR 120 mg once daily for 3 weeks. Unless anginal symptoms had ceased or the investigator felt that the patient could not tolerate a higher dose, daily doses were increased to nisoldipine CC 20 mg and diltiazem CR 180 mg for an additional 3 weeks and then to nisoldipine CC 40 mg and diltiazem CR 240 mg for a final 6-week period. The 2 treatments were found to be equivalent in their effect on total exercise time, which increased significantly from baseline in both cases. In addition, both treatments significantly improved time to onset of angina, time to 1-mm ST-segment depression, weekly rate of angina attacks, and weekly nitroglycerin consumption. No significant between-group differences were noted. The incidence of adverse effects throughout the study was similar in the 2 treatment groups; however, peripheral edema was more common in the nisoldipine CC group than in the diltiazem group. Results of this study suggest that nisoldipine CC and diltiazem CR are equally effective antianginal treatments when given as additional therapy to beta blockers and nitroglycerin in elderly patients with chronic stable angina.

Amlodipine versus diltiazem controlled release as monotherapy in patients with stable coronary artery disease

This study was designed to compare the efficacy and tolerability of amlodipine (5 or 10 mg once daily [QD]) and diltiazem controlled release (CR) (90 or 120 mg twice daily [BID]) as monotherapy in reducing exercise-induced myocardial ischemia. This 8-week, parallel-group, randomized, double-masked study involved 132 patients at 10 outpatient cardiology centers. Patients had proven coronary artery disease confirmed by a typical history of stable angina pectoris, a positive exercise tolerance test, and a positive thallium scan or coronary angiogram. The main outcome measure was a bicycle exercise tolerance test. Median times to 1-mm ST-segment depression increased significantly (16%) for patients in both the amlodipine and diltiazem CR treatment groups. The time to onset of chest discomfort increased significantly after 4 and 8 weeks of treatment by 10% and 12% for amlodipine and by 5% and 7% for diltiazem CR, respectively. Amlodipine also showed a significant increase in median time until end of exercise (5%). However, the difference between treatments was not significant and no between-group differences were noted in anginal attack rates or nitroglycerin consumption. Amlodipine was withdrawn in 3% of patients and diltiazem CR in 9% because of adverse events. Adverse events were reported by 15% of amlodipine-treated patients and 26% of diltiazem CR-treated patients. Although the differences were not statistically significant, there was a trend toward an improved efficacy and safety profile with amlodipine 5 or 10 mg QD compared with diltiazem CR 90 or 120 mg BID in patients with exercise-induced myocardial ischemia.

Management of Ischemic Heart Disease: Therapeutic Options and Future Directions–Official Satellite Symposium to the XVIIth Congress of the European Society of Cardiology

This symposium opened with the presentation of information that will be of assistance in the development of future diagnostic strategies and therapy in angina pectoris. As the principal symptom of ischemic heart disease (IHD), angina requires accurate and prompt diagnosis to enable effective treatment. For example, one common assumption is that a patient may be typically perceived of as a middle-aged man with effort angina, often associated with other illnesses. However, data presented by Dr. Pepine, from a study in 5125 U.S. outpatients, suggests that patients are most likely to be women and the elderly, with high levels of associated illnesses. Despite the availability of a number of surgical and medical therapies, IHD remains a serious health problem. The issue of the relative costs of surgical and medical therapies has been studied by Dr. Cleland through a cost–bene~t and cost-effectiveness analysis model in a hypothetical cohort of 100 patients. The degree of symptom control was a signi~cant determinant in choice of therapy. In patients with well-controlled symptoms, medical therapy offers the most costeffective option. In particular, calcium antagonists, beta-blockers, and long-acting nitrates have formed the mainstay of antiischemic management of IHD. A rational approach to the treatment of chronic myocardial ischemia requires an understanding of the pathophysiology of coronary artery disease and the treatment options available. These two issues are discussed in detail by Dr. Cohn, including the use of combination therapy and new agents under investigation. One of the aims of improving current therapy should be to reduce unwanted interactions, for example, by careful combination of particular classes of drug. Traditional calcium antagonists, in particular, have been associated with a number of side effects, such as headache and _ushing, caused by abrupt vasodilation. The new generation of dihydropyridine calcium antagonists may offer an effective alternative to the original calcium antagonists or beta-blocking drugs because of their improved pharmacodynamic and pharmacokinetic pro~le. This ef~cacy is demonstrated by the multicenter, double-blind study of Dr. van Kesteren, which compared amlodipine with controlled-release diltiazem in 132 patients. The results show bene~ts to both groups of patients, with reduced numbers of withdrawals and adverse events seen in the amlodipine group. Overall, the ef~cacy, tolerability, and once-daily dosing may favor the use of third-generation calcium channel blockers, such as amlodipine, in the treatment of coronary artery disease. Twenty-four hour coverage can improve patient compliance and, more importantly, can provide anti-ischemic control during those periods of the day when there are high rates of ischemic attack. The Circadian Anti-ischemia Program in Europe (CAPE) trial recently showed that, compared with placebo, amlodipine added to background therapy signi~cantly reduced both symptomatic and asymptomatic ischemia over 24 hours in patients with chronic stable angina. The aims of the ongoing CAPE II trial are to compare the effects of amlodipine with diltiazem in treating ischemia, to investigate the ability of these two drugs to manage the circadian pattern of myocardial ischemia, and to evaluate combined therapy of amlodipine plus a betablocker and diltiazem plus a nitrate. The results from this study will demonstrate the optimal medical approach to ischemia suppression in patients with coronary artery disease and add further support to the use of calcium antagonists in future therapeutic recommendations.

Diltiazem controlled-release - effective and well tolerated in hypertension

Diltiazem controlled-release - effective and well tolerated in hypertension

Preparation and dissolution characteristics of controlled release diltiazem pellets

AbstractDifferent series of Diltiazem pellets with slow release of the active substance were prepared, by pan coating technique, using different mixtures of acrylic polymers (Eudragit E, Eudragit L, Eudragit RL and Eudragit RS) as film coating agents. The thickness of the coatings were varied by different amounts of Eudragit. Release profiles of Diltiazem hydrochloride were investigated using USP XX rotating basket method (Erweka DT-D6) with 1000 ml buffer solution (pH values 1.5; 2.2; 5.5; 6.8; 7.0) at 37°C as solvent. In vitro dissolution findings showed that Eudragit coatings gave prolonged release of Diltiazem hydrochloride. The permeability of coatings in gastric and intenstinal juices was found to be influenced by the amount of Eudragit L in the formulation. Also, the drug release rate was found to be dependent on the amount of coating applied. In order to understand the drug release mechanism better, the release data were tested assuming common kinetic models. In the present study square - root of ...

Long-Term Efficacy of Diltiazem Controlled Release Versus Metoprolol in Patients with Stable Angina Pectoris

In a randomized, double-blind, multicenter study, the efficacy of diltiazem controlled-release (CR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 56 patients with stable exertional angina pectoris. Fifty-one patients (28 receiving diltiazem CR, 23 receiving metoprolol), completed a follow-up period of 8 weeks. Thirty-nine patients (20 receiving diltiazem CR, 19 receiving metoprolol), completed a follow-up period of 32 weeks. Maximal exercise testing was performed at baseline and after 8, 20, and 32 weeks of treatment. Most exercise parameters were not significantly different between the patients on diltiazem CR and those on metoprolol. However, exercise duration was longer and maximal work load was higher in patients on diltiazem CR than in patients on metoprolol, and significant differences were observed at 20 weeks of treatment (p = 0.006 and p = 0.008, respectively). At all times during treatment, heart rate at maximal exercise and rate-pressure product at maximal exercise were significantly lower in the patients treated with metoprolol. In conclusion, monotherapy with diltiazem CR is at least as effective as monotherapy with metoprolol in patients with stable angina pectoris. As compared to metoprolol, diltiazem CR has a minor depressing effect on rate-pressure product, resulting in a favorable effect on exercise duration.

Long-Term Efficacy of Diltiazem Controlled Release Versus Metoprolol in Patients with Stable Angina Pectoris

In a randomized, double-blind, multicenter study, the efficacy of diltiazem controlled-release (CR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 56 patients with stable exertional angina pectoris. Fifty-one patients (28 receiving diltiazem CR. 23 receiving metoprolol), completed a follow-up period of 8 weeks. Thirty-nine patients (20 receiving diltiazem CR. 19 receiving metoprolol). completed a follow-up period of 32 weeks. Maximal exercise testing was performed at baseline and after 8, 20, and 32 weeks of treatment. Most exercise parameters were not significantly different between the patients on diltiazem CR and those on metoprolol. However, exercise duration was longer and maximal work load was higher in patients on diltiazem CR than in patients on metoprolol, and significant differences were observed at 20 weeks of treatment (p = 0.006 and p = 0.008. respectively). At all times during treatment, heart rate at maximal exercise and rate-pressure product at maximal exercise were significantly lower in the patients treated with metoprolol. In conclusion, monotherapy with diltiazem CR is at least as effective as monotherapy with metoprolol in patients with stable angina pectoris. As compared to metoprolol, diltiazem CR has a minor depressing effect on rate-pressure product, resulting in a favorable effect on exercise duration.

Controlled release diltiazem improves stable exertional angina

Controlled release diltiazem improves stable exertional angina