Controlled-release Oral Delivery System Research Articles

사포그릴레이트 염산염을 함유하는 신규 OROS 정의 제제 설계 및 용출 거동

Sarpogrelate hydrochloride (SGH) is a drug that improves ischemic symptoms such as ulcers, pain, and feeling of cold caused by chronic arterial occlusion, and has a short half-life of 0.6 to 0.8 hours. Also, reference drug (SarpodipilⓇ SR tablet) is affected by drug release depending on pH. To overcome this, the osmotic controlled release oral delivery system (OROS) utilizes push-pull osmotic pump (PPOP) technology that can achieve zero-order drug release over 24 hours by osmotic pressure. OROS tablet is double-layer tablet consisting of a drug layer (L200-PEO) and a push layer (H5,000- PEO). OROS tablet coated with a semi-permeable film has a orifice of a certain size made by a laser drill, so that the drug is released at a constant rate. The dissolution of the OROS tablet was not affected by the amount of sodium chloride in the drug layer and the number of orifice, but was affected by amount of coating, cellulose acetate (CA) : polyethylene glycol 3350 (PEG 3350) ratio and the size of orifice. Accordingly, as the amount of coating increased and PEG 3350 decreased, the dissolution rate decreased. The developed OROS tablet (formulation C), unlike the reference drug, is not affected by pH, showing high similarity factors of 76.0, 86.1, and 91.2 at pH 1.2, pH 4.0, and pH 6.8 when compared to distilled water. In conclusion, we developed OROS tablet containing SGH, showing zero-order release that continuously releases the drug for 24 hours regardless of pH, and confirmed the factors affecting dissolution.

A comparative evaluation of anti-tumor activity following oral and intravenous delivery of doxorubicin in a xenograft model of breast tumor

PurposeNatural materials have been extensively studied for oral drug delivery due to their biodegradability and other unique properties. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral delivery system that would improve the therapeutic potential of doxorubicin (DOX) and reduce its toxicity.MethodsDOX-loaded NaCNs were synthesized and thoroughly characterized, then subjected to in vivo anti-tumor evaluation and bio-distribution analysis in a 4T1-induced breast cancer model.ResultsOur findings indicated that the tumor would shrink by eight-fold in the group orally treated with DOX-NaCNs when compared to free DOX. The tumor accumulated drug 1.27-fold more from the orally administered DOX-NaCNs compared to the intravenously administered DOX-NaCNs, 6.8-fold more compared to free DOX, and 8.34-times more compared to orally administered free DOX. In comparison, the orally administered DOX-NaCNs lead to a significant reduction in tumor size (5.66 ± 4.36 mm3) compared to intravenously administered DOX-NaCNs (10.29 ± 4.86 mm3) on day 17 of the experiment. NaCNs were well tolerated at a single dose of 2000 mg/kg in an acute oral toxicity study.ConclusionThe enhanced anti-tumor effects of oral DOX-NaCNs might be related to the controlled release of DOX from the delivery system when compared to free DOX and the intravenous formulation of DOX-NaCNs. Moreover, NaCNs is recognized as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumor effects that has a potential for oral chemotherapy.

Febrile seizure during treatment with methylphenidate

Methylphenidate (MPH) is the main psychostimulant drug for children and adolescents with ADHD. The long-acting stimulant of osmotic controlled-release oral delivery system (OROS) MPH has been designed to release gradually increasing concentrations of MPH over a period of 10-12 hours. Febrile seizure (FS) is a seizure associated with high body temperature, typically due to a viral infection. In this case report, a 17-year-old boy with a history of ADHD who experienced a febrile seizure while taking OROS-MPH is reported.

Rational Development of Carbamazepine Osmotic Controlled Release Oral Delivery System for Multiple Therapeutic Advantages

Rational Development of Carbamazepine Osmotic Controlled Release Oral Delivery System for Multiple Therapeutic Advantages

Update on optimal use of lisdexamfetamine in the treatment of ADHD

Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.

Importance of Pharmacokinetic Profile and Timing of Coadministration of Short– and Long–Acting Formulations of Methylphenidate on Patterns of Subjective Responses and Abuse Potential

Objective: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. Methods: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short– (immediate–release [IR] methylphenidate [MPH]) and long– (osmotically controlled—release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR–MPH to IR–MPH; IR–MPH to OROS–MPH; OROS–MPH to IR–MPH; or OROS–MPH to OROS–MPH) in a double–blind, counter–balanced design on 5 separate days. Results: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first–administered long–acting dose (OROS). Conclusion: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short– and long–acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations.

Norepinephrine transporter −3081(A/T) and alpha-2A-adrenergic receptor MspI polymorphisms are associated with cardiovascular side effects of OROS-methylphenidate treatment

The purpose of this study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of the Osmotic Controlled-Release Oral Delivery System-methylphenidate (OROS-MPH) in Korean children with attention-deficit/hyperactivity disorder (ADHD). One hundred and one children with ADHD (8.7 ± 1.7 years) were recruited from child psychiatric centers at six university hospitals in South Korea. All participants were drug-naive ADHD children treated with OROS-MPH for 12 weeks. During the treatment period the investigators titrated the OROS-MPH dosage on the basis of symptom severity and side effects. Resting heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were examined before and after treatment. The percentage change score (post-treatment - pretreatment/pretreatment × 100) of each parameter was calculated. Genotyping of SLC6A2 -3081(A/T) and G1287A, and alpha-2A-adrenergic receptor (ADRA2A) MspI and DraI polymorphisms was performed. Clinically significant changes were not found in cardiovascular monitoring during the course of treatment. An increase of HR after OROS-MPH treatment was found to be statistically significant (t = 3.54, p = 0.001). Changes in SBP and DBP were not significant and no specific change was found in the ECGs. However, an additive regression analysis demonstrated a significant association between SLC6A2 -3081(A/T) and percentage change in HR post-treatment (p = 0.01) after controlling for age, gender, dosage of MPH and response and baseline pulse rate. Children with ADHD having the T/T genotype of SLC6A2 showed a 12.5% increase in HR compared to baseline, whereas children with the A/T or A/A genotype showed a 3.5% and 2.5% increase after OROS-MPH treatment, respectively. There was also a significant association between the ADRA2A MspI genotype and percentage change of DBP post-treatment after controlling for age, gender, dosage of MPH and response and baseline DBP (p = 0.009). Children with ADHD having the C/C genotype of ADRA2A MspI showed an 18.5% increase in DBP compared to baseline, but children with the G/G or G/C genotype showed a 0.2% decrease after OROS-MPH treatment. The overall cardiovascular effects of OROS-MPH were modest. However, our findings show a positive association between norepinephrine-related gene polymorphisms and cardiovascular response induced by MPH in Korean children with ADHD. Consideration must be given to such children or adults with specific norepinephrine-related genotypes, especially if they show significant changes in HR or DBP after OROS-MPH administration.

P02-201 - Safety of the electroconvulsive therapy-paliperidone combination

ObjectivesPatients with psychotic or mood disorders often undergo electroconvulsive therapy (ECT) while receiving antipsychotic and/or other pharmacological agents. Paliperidone (PLP) -a benzisoxazole derivative and the principal active metabolite of risperidone- is a second-generation antipsychotic which has been developed in an osmotic controlled-release oral-delivery system. Thus the peak-through fluctuations of its concentration in plasma are minimized, with consequently decreased incidence of side-effects. To the best of our knowledge, there are, as yet, no reports on the safety of ECT-PLP co-administration.MethodsNine female inpatients suffering from affective disorders (N=7) or schizophrenia (N=2) underwent ECT while receiving PLP (3-12 mg/d). Patients’ regimen included other psychotropic medications as well (mainly antidepressants and/or antipsychotics). All patients were monitored closely for recovery time, post-ictal delirium, cardiological and EEG status for at least one hour after each ECT session. In addition to their clinical evaluation, patients’ cognitive -especially memory- functioning was regularly assessed by the Mini Mental State Examination. Overall, patients underwent 83 sessions of bilateral ECT.ResultsECT-PLP combination was well tolerated and even in cases where cognitive side-effects were of moderate severity (three cases; all were also receiving venlafaxine), they were transient.ConclusionsAlthough anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that ECT and PLP can be safely combined whenever both indicated.

A PET study examining pharmacokinetics and dopamine transporter occupancy of two long-acting formulations of methylphenidate in adults

The delivery systems of two long-acting formulations of methylphenidate (MPH) were designed for different durations. Diffucaps bead-delivery system (DBDS)-MPH was designed to last 8 h and osmotically controlled-release oral delivery system (OROS)-MPH was designed to last 12 h. While the plasma pharmacokinetics and timing of efficacy have been studied, the corresponding central nervous system dopamine transporter (DAT) occupancies are unknown. In this study, 21 healthy volunteers underwent PET imaging with 11C Altropane before and after administration of oral doses of DBDS-MPH and OROS-MPH. Each subject received 40 mg DBDS-MPH and 36 mg OROS-MPH on different days. PET imaging occurred at 10 h after dosing. Each subject was injected with 5 mCi of 11C Altropane and serial images of the brain were acquired over 60 min with a Siemens HR+ PET camera. Binding potentials (BP, k3/k4) were calculated from time-activity curves using the simplified reference region method with cerebellum as reference. Transporter occupancy was calculated by standard methods. At 10 h, plasma d-MPH levels were lower (3.8+/-1.2 vs. 5.2+/-2.0) and brain DAT occupancy was lower (34.8+/-12.9 vs. 44.3+/-11.8) for DBDS-MPH than OROS-MPH. Across the range of values, for each unit of change in plasma d-MPH level there was a larger change in DAT occupancy with the DBDS-MPH formulation than with the OROS-MPH formulation. As predicted from previous pharmacokinetic and efficacy data, the average plasma level and DAT occupancy of 36 mg OROS-MPH was >40 mg DBDS-MPH at 10 h. Moreover, a relatively small difference in plasma levels (1.4 ng/ml at 10 h) was associated with a more impressive difference in DAT occupancy ( approximately 10% at 10 h).

Clinical application of extended-release hydromorphone for pain management

The osmotic controlled-release oral delivery system (OROS®) is being utilized more frequently for once-daily dosing of a variety of medications. While sustained-release formulations of other opioids are currently available in the USA, at present there is no extended-release hydromorphone product on the market. With regard to OROS hydromorphone, a candidate to fill this niche, there is growing evidence to suggest that stable plasma levels can be achieved with tolerable side effects. Furthermore, the drug-delivery system appears to provide reliable opioid release when dosed with food and alcohol.

Health-Related Quality-of-Life Outcomes in Patients Treated with Push-Pull OROS Hydromorphone versus Extended-Release Oxycodone for Chronic Hip or Knee Osteoarthritis Pain

Chronic osteoarthritis (OA) pain impacts health-related quality of life (HR-QOL). The primary aim of this study was to evaluate and compare HR-QOL outcomes following treatment with once-daily push-pull Osmotic controlled-Release Oral delivery System (OROS) hydromorphone versus twice-daily extended-release (ER) oxycodone for moderate to severe chronic knee or hip OA pain. This was a 6-week, randomized, open-label, parallel-group, multicenter study of 124patients with OA whose pre-trial treatment included NSAIDs or other non-steroidal, non-opioid analgesics. The HR-QOL of patients was assessed using the Medical Outcomes Study (MOS) Sleep Scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™). Within- and between-group changes from baseline to 6weeks were evaluated using ANOVA. At baseline, trial patients had significantly worse MOS Sleep Scale (multivariate ANOVA [MANOVA] F = 11.0, p < 0.001) and WOMAC™ scores (MANOVA F = 55.7, p < 0.001) than chronic disease benchmarks. Both treatment groups showed significant improvements on the sleep disturbance scale (p < 0.01), with additional improvements observed with OROS hydromorphone on the sleep quantity (p = 0.046), sleep snoring (p = 0.044), awaken short of breath or with a headache (p = 0.024), 6-item sleep problems index I (p < 0.001), and 9-item sleep problems index II (p < 0.001) scales. Significant treatment differences in favor of OROS hydromorphone over ER oxycodone were also observed on the awaken short of breath or with a headache (p = 0.014) scale and sleep problems index I (p = 0.045). Both treatment groups showed comparable large effect size (>0.8 SD unit) improvements on the WOMAC™ scale (measuring functionality outcomes such as pain, stiffness, physical function etc). Both OROS hydromorphone and ER oxycodone improved sleep and function, with greater sleep benefits being observed in patients treated with OROS hydromorphone.

Comparative bioavailability of single-dose methylphenidate from a multilayer-release bead formulation and an osmotic system: A two-way crossover study in healthy young adults

Objective: This study was conducted to compare plasma levels of methylphenidate over time with single doses of a multilayer-release (MLR) bead formulation and an osmotic, controlled-release oral delivery system (OROS) of methylphenidate in young adults. Methods: This was a randomized, 2-way crossover study in which healthy, nonsmoking young adults (age 18-25 years) were randomized to receive methylphenidate MLR 20 mg QD or OROS methylphenidate 18 mg QD, with a 7-day washout between treatments. Plasma samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 14, 16, and 24 hours after dosing. Analysis of plasma samples was conducted by high-performance liquid chromatography with tandem mass-spectrometry detection. Adverse events were monitored by spontaneous reports, laboratory and biochemistry tests, urinalysis, and physical examinations conducted at screening and at the end of the study. Results: Of the 24 subjects originally enrolled, 3 discontinued for personal reasons after the first phase and were not included in the pharmacokinetic analysis. The per-protocol population (11 females, 10 males) had a mean (SD) age of 22 (2) years (range, 19-25 years) and a mean body mass index of 23.6 (3.0) kg/m 2 (range, 19.0-28.5 kg/m 2). The relative AUC0t and Cmax ratios for the MLR methylphenidate formulation compared with the OROS methylphenidate formulation were 110.88% and 121.84%, respectively. When OROS methylphendate values were dose normalized to 20 mg, the relative AUC0-t and Cmax ratios were 100.72% and 111.82%. The mean Tmax for the 2 formulations was 3.71 (2.03) and 4.96 (2.56) hours. Values were significantly higher with the MLR methylphenidate formulation compared with the OROS methylphenidate formulation for AUC 0-4 ( P < 0.001), AUC 0-8 (P < 0.001), AUC 0-12 ( P < 0.001), and AUC 4-12 ( P = 0.037); the AUC 8-12 was not significantly different between the 2 formulations. Values were significantly higher for the MLR methylphenidate formulation relative to the OROS methylphenidate formulation for C max0-4 ( P < 0.001) and C max4-12 (P = 0.002). Thirty-seven adverse events occurred in 11 and 10 subjects during receipt of MLR and OROS methylphenidate, respectively. The most commonly reported adverse events in the intent-to-treat population were catheter-site pain, reported by 8 of 24 subjects (33.3%), and headache, reported by 5 of 24 subjects (20.8%). Conclusions: In these healthy young subjects, MLR methylphenidate was associated with a concentration-time profile that resulted in a higher proportion of the administered methylphenidate dose being delivered in the first 4 hours after dosing compared with OROS methylphenidate while maintaining comparable levels of drug in the latter portion of the dosing interval. This led to maintenance of higher mean levels of methylphenidate throughout the day compared with the closest marketed dose of OROS methylphenidate. The 2 formulations are marketed in dissimilar strengths; however, after correction for administered dose, they yielded similar AUC values.

The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia

Paliperidone extended-release (ER) is a newly commercialised antipsychotic formulated using the principal active metabolite of risperidone, 9-hydroxyrisperidone. It has been developed as an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and theoretically leading to a decreased incidence of adverse effects. Available data from preregistration, multicenter, short-term, double-blind, placebo-controlled studies indicate that paliperidone ER, at dosages of 3 – 15 mg/day, is relatively safe and well tolerated in adult patients with schizophrenia. As with risperidone, paliperidone may cause extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner. Preliminary long-term studies (up to 52 weeks) appear to confirm the findings from short-term trials indicating a low liability for paliperidone ER to cause metabolic effects (i.e., weight gain, hyperglycaemia and lipid dysregulation). Safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug–drug interactions.

Modeling the economic and health consequences of managing chronic osteoarthritis pain with opioids in Germany: comparison of extended-release oxycodone and OROS hydromorphone

ABSTRACTObjective: The Osmotic controlled-Release Oral delivery System (OROS) hydromorphone ensures continuous release of hydromorphone over 24 hours. It is anticipated that this will facilitate optimal pain relief, improve quality of sleep and compliance. This simulation compared managing chronic osteoarthritis pain with once-daily OROS hydromorphone with an equianalgesic dose of extended-release (ER) oxycodone administered two or three times a day.Methods: This discrete event simulation follows patients for a year after initiating opioid treatment. Pairs of identical patients are created; one receives OROS hydromorphone the other ER oxycodone; undergo dose adjustments and after titration can be dissatisfied or satisfied, suffer adverse events, pain recurrence, or discontinue the opioid. Each is assigned an initial sleep problems score, and an improved score from a treatment dependent distribution at the end of titration; these are translated to a utility value. Utilities are assigned pre-treatment, updated until the patient reaches the optimal dose or is non-compliant or dissatisfied. The OROS hydromorphone and ER oxycodone doses are converted to equianalgesic morphine doses using the following ratios: hydromorphone to morphine ratio; 1:5, oxycodone to morphine ratio; 1:2. Sensitivity analyses explored uncertainty in the conversion ratios and other key parameters. Direct medical costs are in 2005 euros.Results: Over 1 year on a mean daily morphine-equivalent dose of 90 mg, 14% were estimated to be dissatisfied with each opioid. OROS hydromorphone was predicted to yield 0.017 additional quality-adjusted life years (QALYs)/patient for a small additional annual cost (€141/patient), yielding an incremental cost-effectiveness ratio (ICER) of €8343/QALY gained. Changing the assumed conversion ratio for oxycodone:morphine to 1:1.5 led to lower net costs of €68 per patient, €3979/QALY, and for hydromorphone to 1:7.5 to savings.Conclusion: Based on these analyses, OROS hydromorphone is expected to yield health benefits at reasonable cost in Germany.

Mapping MOS Sleep Scale scores to SF‑6D utility index

ABSTRACTObjective: Deriving preference scores for the Medical Outcomes Study (MOS) Sleep Scale would enable its use in cost–utility analyses. The objective of this study was to map scores of the MOS Sleep Scale to a preference-based health-state utility index (SF‑6D) scored from the SF‑36 Health Survey (SF‑36).Research design and methods: Three datasets were used: (1) the MOS study, a 4-year observational study of chronically ill patients, (2) a 7-week open-label, non-comparative clinical trial of an osmotic controlled-release oral delivery system (OROS) hydromorphone in the treatment of chronic low back pain (CLBP), and (3) a 6-week open-label randomized controlled trial of OROS hydromorphone in the treatment of pain associated with chronic osteoarthritis (OA). Various models were tested, where SF‑6D was regressed onto the Sleep Problem Index‑II (SLP9) in 1000 random half (developmental) samples of the MOS (n = 1413). The best fitting model was applied to the other 1000 random half (cross-validation) samples of the MOS (n = 1412), and to the two trial samples (n = 199 in the CLBP trial; n = 124 in the OA trial).Results: The best fitting model in the MOS samples included a quadratic term for the SLP9 which explained 34% of the variance in SF‑6D in the developmental samples. Errors in prediction were greatest at higher SLP9 scores. Addition of demographic and clinical variables to the model explained minimal incremental amounts of variance (< 5%) in SF‑6D scores. These results were replicated in the cross-validation MOS samples. In both developmental and cross-validation MOS samples, mean predicted and observed SF‑6D scores were nearly identical. When the mapping algorithm developed in the MOS was applied to the CLBP sample, mean predicted SF‑6D scores were 0.09 points higher than observed SF‑6D scores at both baseline and final visits, while changes in predicted and observed SF‑6D scores were identical.Conclusion: Results indicate that it is possible to map MOS SLP9 to SF‑6D yielding useable preference-based scores essential for cost–utility analyses. A limitation concerns the interpretation of SF‑6D scores estimated from SLP9 scores above 60, where the prediction errors increased considerably.

Extended-release paliperidone: Efficacy, safety and tolerability of a new atypical antipsychotic

Extended-release paliperidone is a new atypical antipsychotic chemically related to the well-known antipsychotic risperidone. It has been formulated in an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations and, by obviating dose-titration, allows once-daily dosing with a therapeutically active dose from the first day. Its pharmacokinetic profile is characterized by a mean time-to-peak plasma concentration of 24.1 hours and an elimination half-life of approximately 24 hours. A dose of 6 mg of paliperidone extended-release (ER) provides a mean striatal D2 receptor occupancy of 64%, approaching the accepted lower receptor occupancy threshold required for optimal antipsychotic activity without causing extrapyramidal symptoms. It undergoes minimal hepatic biotransformation and is mainly excreted unchanged in the urine with four metabolic products. Three pivotal randomized, double-blind, placebo-controlled, parallel-group six-week trials investigated the efficacy, safety and tolerability of paliperidone ER at doses of 3-15 mg/day. All doses produced a significant reduction in schizophrenia symptomatology, with an onset of effect as of day 4. Personal and social functioning also improved as measured by the Personal and Social Performance scale. A prevention of recurrence study showed that paliperidone ER effectively prolonged the time-to-recurrence versus placebo. Paliperidone ER was efficacious in young, elderly and recently diagnosed schizophrenia patients. Beneficial effects on sleep assessed objectively and subjectively with minimal daytime somnolence were demonstrated. Overall, it was well-tolerated and had placebo-like discontinuation rates for adverse events. There were some dose-related extrapyramidal symptoms, mostly mild to moderate in intensity and associated with minimal changes in the rating scales that assessed extrapyramidal symptom severity. Although prolactin elevation occurred with paliperidone ER, only few prolactin-related adverse events were reported. There were no signals for metabolic dysfunction in terms of glucose, insulin, lipid or triglyceride changes or any indicators of clinically relevant cardiac events. Body weight increased slightly, but the changes were acceptable in the context of the doses likely to be used clinically, and patients with higher initial body mass index gained less weight as has been reported for other antipsychotics.

염산 탐스로신을 함유하는 방출제어형 제제의 제조 및 용출거동

As a selective antagonist, tamsulosin has been used clinically for urinary obstructed patients with benign prostatic hyperplasia. The single and multi-layered pellets containing tamsulosin hydrochloride were prepared in an effort to control the drug release, avoiding dose-dependent side effects of tamsulosin hydrochloride upon oral administration. The drug release from multi-layered pellets was substantially controlled, compared with single layered pellets. The drug release from coated pellets with single or multi layer was affected by the nature of coating agent, the percentage of coating level and the presence of hydrophilic material in coating layer. In conclusion, the controlled release oral delivery system using multi-layered pellet is very useful for tamsulosin hydrochloride, resulting in improvement of patient compliance and therapeutic drug levels for a longer period of time.