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@#As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (Papp), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.
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Objective: To discuss the diagnosis and treatment process of abnormally elevated blood pressure in the patient treated with rifampicin and antihypertensive drugs, to analyze the interaction between rifampicin and antihypertensive drugs, and to improve the clinicians' understanding of the administration in the patients. Methods: The clinical materials of a patient treated with rifampicin and antihypertensive drugs were collected, and the relationship between the blood pressure change and drug was analyzed. The changes of concentrations of dihydropyridine-based calcium antagonists after administration of rifampin were observed and the relative literatures were reviewed. Results: A 58-year-old man with coughing and coughing for 1 month was admitted to hospital. The patient was definitely diagnosed as tuberculosis and hypertension before admission; the patient was treated with rifampicin, isoniazid, ethambutol, pyrazinamide, and felodipine together. The original treatment plan was continued and the blood pressure of the patient was monitored. On the 9th day of anti-tuberculosis treatment, the patient developed dizziness, chest tightness, and severe fluctuations in blood pressure. Then rifampicin was stopped and antihypertensive drugs were adjusted. At the beginning of blood pressure fluctuation of the patient, the combination of angiotensin-converting enzyme inhibitors and the increasing dose of dihydropyridine-based calcium antagonists did not control the blood pressure. The blood pressure began to decrease significantly at 36 h after rifampin was stopped. On the 18th day of anti-tuberculosis treatment, the original antihypertensive plan was restored and the blood pressure remained stable. Conclusion: Rifampicin can sometimes significantly reduce the effect iveness of antihypertensive drugs (such as dihydropyridine calcium antagonists), and the clinicians should pay attention to it.
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OBJECTIVE: To clarify the crystal forms of the active pharmaceutical ingredient and preparations of felodipine from different sources, and explore the relationship between quality and efficacy of felodipine and its crystal form. METHODS: Crystal form characterization of the active pharmaceutical ingredient from different sources was carried out by powder X-ray diffraction (PXRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The Origin software was used to analyze the crystal forms of felodipine in the sample preparations from different sources. Biological evaluation in vivo was conducted by using whole animals. RESULTS: There were some differences in the crystal state of the active pharmaceutical ingredient from different sources, but the main components were basically the same, all of which were type I. Biological studies showed significant differences in the main pharmacokinetic parameters of felodipine sustained release tablets from different sources. Among them, the ρmax, tmax, t1/2, and AUC0-t had maximal 1.8, 1.4, 8.2 and 1.5 times of differences. CONCLUSION: Although the main crystal forms of felodipine bulk drug from different origins are consistent, the crystal state significantly changes after the preparation process. This finding is of important scientific significance to guide the improvement of process and product quality.
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OBJECTIVE:To observe clinical efficacy of Felodipine sustained-release tablets(Ⅱ)in the treatment of elderly es-sential hypertension and its improvement effect on arterial elasticity,left ventricular remodeling and the quality of life. METHODS:A total of 96 elderly patients with essential hypertension in our hospital during Aug. 2014-Dec. 2015 were divided into observation group (50 cases) and control group (46 cases) according to random number table. Observation group was given Felodipine sus-tained-release tablets(Ⅱ)5 mg orally,qd,with empty stomach in the morning;control group was given Irbesartan tablets 150 mg, qd,with empty stomach in the morning. Both groups received treatment for 12 weeks. Clinical efficacies of 2 groups were observed as well as 24 h ambulatory blood pressure (ABP),indexes of arlerial elasticity [carotid-radial pulse wave velocity (CR-PWV),carot-id-femoral pulse wave velocity (CF-PWV)], indexes of left ventricular remodeling [diastolic interventricular septum thickness (IVST),diastolic left ventricular posterior wall thickness(LPWT),left ventricular end diastolic diameter(LVIDd)] before and after treatment. The physiological function (PF),social function (SF),role-physical (RP),body pain (BP),mental health (MH),role-emotional(RE),vitality(VT)and general health(GH)score of SF-36 were observed in 2 groups before and after treatment. The occurrence of ADR was compared between 2 groups. RESULTS:There was no statistical significance in total response rate be-tween 2 groups (P>0.05). There was no statistical significance in 24 hABP,CR-PWV,CF-PWV,IVST,LPWT,LVIDd,SF-36 score between 2 groups before treatment(P>0.05). After treatment,the levels of 24 hSBP,24 hDBP and 24 hMAP in 2 groups were decreased significantly,and 24 hSBP and 24 hMAP of observation groups were significantly lower than those of control group,with statistical significance (P0.05). The levels of CR-PWV,CF-PWV, IVST and LPWT in observation group were decreased significantly,and the levels of CR-PWV and LPWT in control group were also decreased significantly. The levels of CR-PWV,CF-PWV,IVST,LPWT and LVIDd in observation group were significantly lower than control group,with statistical significance (P0.05). CONCLUSIONS:Felodipine sustained-release tablets(Ⅱ)exhibit significant effect and small blood pres-sure fluctuation in the treatment of elderly essential hypertension,and can improve the quality of life with good safety.
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Liquisolid formulation involves dissolution or dispersion of the drug in a liquid before formulation of solid dosage form using solid adsorbent as a carrier. The liquid component usually utilizes simple solvent system. Self emulsifying liquids can provide another alternative liquid for enhanced dissolution. The objective of this work was to develop and evaluate non-self emulsifying and self emulsifying liquisolid tablet for enhanced dissolution rate of felodipine. The former utilized polyethylene glycol 400 which was the best solvent and the later employed a mixture of castor oil with labrasol and transcutol as self emulsifying system. A mixture of avicel PH 102 and aerosil 200 was used as solid adsorbent with croscarmellose being used as superdisintegrent. Formulation of the drug as liquisolid tablets enhanced the dissolution rate compared with the standard tablet prepared using the unprocessed drug powder with the same tablet excipients. The self emulsifying tablet showed faster release pattern compared with the non-self emulsifying tablet. The thermal analysis studies indicated the presence of the drug in a solution form in the tablet formulations. In conclusion liquisolid tablet formulation can enhance the dissolution rate of felodipine with self emulsifying liquid system being more efficient.
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Objective:To explore therapeutic effect of felodipine combined atorvastatin on aged patients with isolated systolic hypertension (ISH).Methods:A total of 176 aged ISH patients were selected from our hospital from Mar 2012 to Jan 2014. They were randomly and equally divided into felodipine group (only received felodipine and other routine therapy)and combined treatment group (received atorvastatin based on treatment of felodipine group),both groups were treated for 12 weeks.Levels of systolic blood pressure (SBP),diastolic blood pressure (DBP),pulse pressure (PP),fore brachial artery endothelium dependent diastolic-systolic function (FMD),nitric oxide (NO), high sensitive C reactive protein (hsCRP)and interleukin (IL)-6 were measured and compared between two groups before and after treatment.Results:Compared with before treatment,after treatment there were significant reductions in levels of SBP,PP,hsCRP and IL-6,and significant rise in FMD and NO level in both groups (P<0.01 all).Compared with felodipine group after treatment,there were significant reductions in levels of SBP [(134.64 ±9.64)mmHg vs.(130.86±9.75)mmHg],PP [(68.57±6.01)mmHg vs.(57.84±5.79)mmHg],hsCRP [(11.94±2.95)mg/L vs.(7.47±1.97)mg/L]and IL-6 [(10.64±3.85)mg/L vs.(5.84±3.11)mg/L],and sig- nificant rise in DBP [(72.64±7.95)mmHg比 (77.94±8.13)mmHg]and FMD [(9.75±2.56)% vs.(12.54± 4.65)%]and NO [(53.74±8.65)μmol/L vs.(86.48±6.84)μmol/L]in combined treatment group,P<0.05 or<0.01. Conclusion:Felodipine combined atorvastatin possesses good therapeutic effect in aged patients with isolated systolic hypertension.It' s help to recovering vascular function and lower inflammatory reactions.
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OBJECTIVE:To investigate the effects of hydrophilic polymers on the stability of self-microemulsifying drug deliv-ery systems (SMEDDS). METHODS:Taking felodipine (FDP) as model drug,the content of FDP was determined by HPLC method. The effects of pure water,0.5% Kollidon VA64,HPMC E5,HPMC K100LV,HPMC K4M,PVP K30 solution,while 0.1%,0.5% and 1.0% HPMC E5 and Kollidon VA64 on residual content of dissolved FDP were determined in SMEDDS. RE-SULTS:The residual contents of dissolved FDP in SMEDDS placed in Kollidon VA64,HPMC E5,HPMC K100LV,PVP K30, HPMC K4M and pure water for 1 h were 92.7%,63.6%,50.2%,46.2%,36.0%and 24.0%,respectively. The order of maintain-ing the supersaturation state was Kollidon VA64>HPMC E5>HPMC K100LV>PVP K30>HPMC K4M>pure water. The residu-al contents of dissolved FDP in SMEDDS placed in 0.1%,0.5%,1% Kollidon VA64 and HPMC E5 and pure water for 1 h were 93.2%,95.1%,96.0% and 48.4%,62.1%,75.1%. CONCLUSIONS:Kollidon VA64 and HPMC E5 can significantly inhibit drug release in SMEDDS and be used as stabilizer of SMEDDS,wherein Kollidon VA64 was better.
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Objective:To develop the uniformity models for felodipine sustalned-release tablets from 3 manufacturers by NIRS in order to study the difference in the preparation technology and detect and screen the tablets quickly by the robust, accurate and repre-sentative models. Methods:The uniformity models for the tablets from 3 manufacturers among 6 manufacturers with evaluative casual inspection were established by NIRS. Region 4 000-9 000 cm-1 was chosen as the modeling section, and the first derivative plus vector normalization was used as the preprocessing method. Results:The uniformity models for the tablets from the three manufacturers was established and used to predict the samplings from the six manufacturers. The prediction success rate was 100%. Conclusion: NIRS can be used to identify felodipine sustalned-release tablets from different manufacturers quickly and study the preparation technology.
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OBJECTIVE: To establish an HPLC method for determining the contents and related substances of felodipine and metoprolol tartrate in compound felodipine sustained-release tablets. METHODS: The analysis of felodipine was performed on an Agilent Eclipse XDB-C18 column (4.6 mm × 150 mm, 5 μm), using a mobile phase of methanol-acetonitrile-water (50:20:30) at the flow rate of 1.0 mL · min-1. The column temperature was maintained at 25℃. The detection wavelength was set at 238 nin and injection volume was 20 μL. The analysis of metoprolol tartrate was performed on an Agela Venusil MP C18 column (4.6 mm × 150 mm, 5 μm), using a mobile phase of 0.48% ammonium acetate (pH adjusted to 7.5 with triethylamine and glacial acetic: acid)-acetonitrile-methanol (65:20:15) at the flow rate of 1.0 mL · min-1. The column temperature was maintained at 30℃. The detection wavelength was set al 275 nm and injection volume was 20 μL. RESULTS The linear ranges of felodipine and metoprolol tartrate were 0.005-0.06 mg · mL-1 and 0.05-0.60 mg · mL-1, respectively. The average recoveries of felodipine and metoprolol tartrate were 100.70% and 99.62%, respectively. The RSDs of this method were all less than 2% (n=9). CONCLUSION: The method is applicable for the contents and related substances control of compound felodipine sustained-release tablets.
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The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.
O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.
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Felodipine/pharmacokinetics , Drug Liberation/drug effects , Emulsifying Agents/pharmacokinetics , Emulsions/pharmacokinetics , Drug Chronotherapy , Hypertension/prevention & controlABSTRACT
Objective To investigate the clinical efficacy of felodipine combined with irbesartan in the treat-ment of hypertension and its effect on atherosclerosis in remission .Methods 100 patients with hypertension were divided into the observation group and the control group .The control group was given the felodipine treatment ,the obser vation group was given felodipine treatment based on the control group .The treatment effect ,changes of blood control and carotid artery intima-media thickness were compared between the two groups .Results The total effective rate of the observation group was 90.0%,which was significantly higher than 72% of the control group (χ2 =3.85,P<0.05).After treatment,the systolic pressure,diastolic pressure of the observation group were significantly lower than those in the control group(t=4.21,5.05,all P<0.05).After treatment,the size,thickness of carotid artery plaque of the observation group were significantly lower than those of the control group (t =1.98,5.05,all P <0.05). Conclusion Felodipine combined with irbesartan can significantly improve the therapeutic effect of hypertensive patients,and can improve the control of blood pressure ,slow the progression of atherosclerosis .
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OBJECTIVE: To solve the stability problem of felodipine nanosuspension which is a physically unstable colloidal dispersion by solidification method.
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Objective To study the therapeutic effect of diltiazem and felodipine in treatment of hypertension after renal transplantation.Methods Sixty patients with hypertension after renal transplantation who were treated with tacrolimus as basic immunosuppressive therapy were divided into two groups by random digits table method with 30 cases each.The diltiazem group took diltiazem 90 mg orally once a day.The felodipine group received felodipine 2.5 mg orally twice a day.The drug dosages were adjusted according to the level of blood pressure.The patients were followed up for 1 year.The artery pressure,concentration-to-dose ratio of tacrolimus and renal function was detected and compared.Results Blood pressure was significantly decreased in both groups after 1 year treatment.Blood pressure was found to be significantly lowered from (153.6± 7.5)/ (97.7 ±6.7) mm Hg (1 mm Hg=0.133 kPa) to (119.1 ± 26.4)/ (72.6± 19.3) mm Hgin felodipine group; and from (152.0 ± 7.6)/(95.4 ± 6.9) mm Hg to (120.3 ± 25.5)/(73.2 ± 22.5) mm Hg in diltiazem group.There was no significant difference in blood pressure before and after treatment between two groups (P ＞ 0.05).The concentration-to-dose ratio of tacrolimus was increased after treatment in diltiazem group[(173.2 ± 59.3) g/L vs.(119.3 ± 78.3) g/L] (P ＜ 0.05),but there was no significant difference before and after treatment in felodipine group (P ＞ 0.05).The serum creatinine had no significant difference in two groups (P ＞ 0.05).Conclusion Diltiazem and felodipine can be used safely and effectively in the treatment of hypertension after renal transplantation,and diltiazem can lower the dose of tacrolimus.
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OBJECTIVE: To establish an HPLC method to determine the dissolutions of felodipine and metoprolol tartrate in compound felodipine controlled release tablets. METHODS: An HPLC method was established with Agilent Eclipse C18 column (4.6 mm×250 mm, 5 μm).A mixture of 0.3% SDS (pH adjusted to 2.5 with phosphoric acid)-acetonitrile-methanol V:V:V(40:50:10) was used as the mobile phase. The column temperature was 25°C. The flow rate was 1 mL·min-1 and the detection wavelength was set at 233 nm. RESULTS: The relative retention time of felodipine and metoprolol tartrate was 6.20 and 8.45 min respectively. The linear ranges of these two drugs were 1-24 μg·mL-1 (r=0.9999) and 10-240 μg·mL-1 (r=0.9999). The average recoveries of felodipine and metoprolol tartrate were 99.99% and 99.91% respectively. The RSDs of this method were all less than 2%. CONCLUSION: The established method is sensitive, accurate and reliable for determination of the dissolutions of felodipine and metoprolol tartrate in compound felodipine controlled release tablets.
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Felodipine is a calcium channel blocker that is used in the management of hypertension. Calcium channel blockers, along with phenytoin and cyclosporin, are implicated as a cause of gingival hyperplasia. Calcium channel blockers associated with this undesired side-effect include nifedipine, nicardipine, isradipine, amlodipine, felodipine, verapamil, and diltiazem. Several cases of adverse gingival hyperplasia related to felodipine have been reported since 1991, although no case has been reported in Korea. We report a case of gingival hyperplasia in a 55-year-old man on long-term felodipine.
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Humans , Middle Aged , Amlodipine , Calcium Channel Blockers , Calcium Channels , Cyclosporine , Diltiazem , Felodipine , Gingival Hyperplasia , Hypertension , Isradipine , Korea , Nicardipine , Nifedipine , Phenytoin , VerapamilABSTRACT
OBJECTIVE:To evaluate the cost-effectiveness of telmisartan in combination with different drugs in the trea-tment of mild to moderate essential hypertension.METHODS:A total of 60 patients were enrolled and randomized to Group A(telmisartan+felodipine),Group B(telmisartan+enalapril),or Group C(telmisartan+indapamide).A cost-effectiveness analysis of the three therapeutic schemes was conducted after 8-wk treatment.RESULTS:The effective rates of three Groups were 90%,85% and 95%,respectively;the total costs of three groups were 422.80,409.50 and 348.88 yuan,respectively,with Group C showing significant difference as compared with the other two groups(Group B and Group C)(P
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Objective To compare the efficacy of valsartan,benazepril and felodipine on reversal of left ventricular hypertrophy(LVH)in patients with hypertension and the relevant "aldosterone escape phenomena".Methods One hundred eleven patients with hypertension-related LVH were randomly to receive valsartan(80-160 mg/d,n=36),benazepril(10-20 mg/d,n=39)and felodipine(5 mg/d,n=36).Plasma angiotensin Ⅱ(Ang Ⅱ)and aldosterone(Ald)were determined before and 10-14 weeks 20-26 weeks after treatment.Echocardiographic examinations and blood routine,urine routine,blood glucose,blood lipid,liver function and renal function were conducted in all subjects before and after treatment.Results Blood pressure was significantly decreased in all three groups(P0.05).Valsartan increased plasma Ang Ⅱ at 10-14 weeks and furthermore at 20-26 weeks;benazepril decreased plasma Ang Ⅱ initiatively with trend of rebound at 20-26 weeks;however,plasma Ang Ⅱ was kept constantly in felodipine group.Valsartan decreased Ald and sustained during the all treatment period.On contrary,benazepril initiatively decreased Ald which was rebound to baseline level at 20-26 weeks.No change in Ald by felodipine was found during the treatment.After treatment plasma Ald level was significantly related to the reduction of LVH in both valsartan and benazepril groups.36% patients in benazepril group was found to have "aldosterone escape".Conclusion The antihypertensive effect was similar between valsartan,benazepril and felodipine.Although three medications all reversed LVH,but valsartan,benazepril was more effective than felodipine.There was no evidence of aldosterone escape in the long-term treatment with valsartan.Valsartan might have more advantages in reversal of LVH than benazepril.Felodipine had no effect on the plasma level of aldosterone.
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OBJECTIVE:To provide reference for the standardization of the instructions of felodipine.METHODS:The instructions of felodipine in China were compared with the national regulation as well as foreign instructions of felodipine.The problems of Chinese instructions of felodipine were analyzed to put forward revision measures.RESULTS & CONCLUSIONS:The problems of Chinese instructions of felodipine are items shortage or missing,lacking of warnings for drug safety.It is suggested that related administration departments and enterprises should revise and improve the instructions of felodipine.
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OBJECTIVE:To observe the effects of gelodipine on plasma ghrelin level and endothelial function of blood vessels in patients with essential hypertension.METHODS:A total of 77 patients with essential hypertension were randomly divided into trial group(n=45)and control group (n=32).Both groups were given low sodium diet,proper exercise, weight reduction and oral diuretics,while the trial group was assigned to receive felodipine 5mg q.d additionally.The course of treatment was 8wk.Before and after the treatment,plasma levels of ghrelin and nitrous oxide(NO),endothelin(ET-1),and brachial artery flow-mediated dilatation(FMD)function were observed.RESULTS:Plasma levels of ghrelin and NO,and FMD were significantly increased (P0.05).CONCLUSION:Felodipine can increase plasma Ghrelin level meanwhile improving endothelial function of blood vessels in patients with essential hypertension.
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OBJECTIVE:To observe the effects of felodipine on blood vessel endothelial function in patients with benign prostatic hyperplasia(BPH) complicating essential hypertension(EH).METHODS:Fifty five patients with BPH complicating EH were assigned to receive 5mg felodipine orally qd for 6 weeks,with levels of endothelin-1(ET-1),nitrous oxide(NO) and von Wilebrand factor(vWF),brachial artery flow-mediated dilatation(FMD) function,the maximum urine flow rate,the average urine flow rate and International Prostate Symptom Score(I-PSS) determined before and after treatment.Meanwhile levels of ET-1,NO and vWF and FMD in 37 normal healthy males were determined.RESULTS:In the treatment group compared with normal control group there were significant differences in levels of ET-1,NO and vWF and FMD(P0.05).There were significant differences in ET-1,NO and vWF levels and FMD after treatment as compared with before treatment(P