Sustained-release Capsules Research Articles

Preparation and Evaluation of Sustained Release Calcium Alginate Beads and Matrix Tablets of Acetazolamide

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Observation on Pain Release by Long-Round Needle Therapy in Knee Osteoarthritis Related with Meridian-Sinews Theory

To evaluate the effectiveness of long-round needle therapy for pain relief in patients with knee osteoarthritis, 192 patients were included in a multicenter, randomized, controlled trial. 97 patients were randomized to the long-round needle therapy group (EG), and 95 patients were randomized to the control group (CG). In EG, the long-round needle therapy was performed once every 7 days for 3 therapy sessions. Ibuprofen sustained-release capsules were administered orally in CG, 1 pill each time, twice daily for 3 weeks. Curative effect was measured after the therapy and was evaluated at a 3-month follow-up interview. In EG, the treatment resulted in a basic cure for 79 patients, was effective for 15 patients, and was ineffective for 1 patient. In CG, the treatment resulted in a basic cure for 30 patients, was effective for 38 patients, and was ineffective for 21 patients. In the follow-up examination in EG, 75 patients were basically cured, and the treatment was effective for 11 patients and ineffective for 9. In CG, 22 were basically cured, 31 found the treatment effective, and 36 found the treatment ineffective. The curative effects in EG after both the treatment and the 3-mouth followup were significantly more superior than that in CG (P < 0.01) which should be adopted more widely.

A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f2 > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC0–36 and Cmax ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol® SR capsule.

Bidirectional Sex Change Induced by Sex Steroid Implantation in the Hermaphrodite Fish, Pseudolabrus sieboldi

Sex steroids have been suggested to be involved in gonadal sex change in hermaphrodite fish. Aromatase, the enzyme that catalyzes the conversion of androgens into estrogens, is a principal enzyme regulating gonadal sex. However, the detailed functions of each steroid hormone remain to be evaluated. Recent studies have demonstrated that estradiol-17β (E2) is synthesized via estrone (E1) in some hermaphrodite species. On the other hand, 11-ketotestosterone (11KT) is produced in the testis via testosterone (T). In this study, we hypothesized that E1 and T are also involved in the sex change as precursors for E2 and 11KT, respectively. We implanted females of the wrasse, Pseudolabrus sieboldi, with T and 11KT, and males with E1 and E2, by use of sustained-release capsules. In females, testicular tissues and body color change were observed after androgen administration, in which 11KT was more effective than T. In contrast, after estrogen administration, the gonads of males contained oocytes. In females, the administration of T and 11KT resulted in reduced serum E2 levels. Conversely, serum 11KT levels decreased in the E1- and E2-treated males. Thus, we successfully induced bidirectional sex change in the gonad by estrogen and androgen administration in vivo. Moreover, this study raises the possibility that E1 and T are involved in the sex change as precursors for E2 and 11KT, respectively.

Roxithromycin for multidrug-resistant pulmonary tuberculosis

Objective To observe and assess the efficacy of roxithromycin sustained-release capsules com-bined with other anti-tuberculosis drugs in the treatment of multidrug-resistant pulmonary tuberculosis ( MDR-PTB ).Methods 120 patients with MDR-PTB were selected as the subjecs of this study and then were randomly divided intostudy group and control group,60 for each group.The control group received sparfloxacin,amikacin,and other three kindsof anti-tuberculosis drugs as anti-tuberculosis scheme,and the study group received roxithromycin for 12 months inaddition to the therapies used in the control group.Results At the end of the third month,the sputum negative conversionrate was 64％ in the study group and 42％ in the control group,with a statistical significance ( ~=5.52,P＜ 0.05 ).Atthe end of treatment,the sputum negative conversion rate was 91％ in the study group and 72％ in the control group,witha significant difference ( x2=6.62,P＜ 0.01 ).The rate of lesion absorption was 89％ in the study group and 70％ in thecontrol group,with a statistical significance ( x2=6.14,P ＜ 0.05 ).Conclusions Roxithromycin sustained-releasecapsules combined with other anti-tuberculosis drugs is efficacious in the treatment of MDR-PTB and plays a role inpromoting sputum negative conversion,lesion absorption,and cavity closure. Key words: Tuberculosis, pulmonary; Multidrug resistance; Roxithromycin sustained-release capsules; Efficacy

A Randomized, Single-Center Double-Blinded Trial on the Effects of Diltiazem Sustained-Release Capsules in Patients with Coronary Slow Flow Phenomenon at 6-Month Follow-Up

ObjectiveThe aim of this study is to observe the chronic effects of diltiazem release capsules on patients with coronary slow flow (CSF) phenomenon.MethodsFrom 2004 to 2009, 80 consecutive patients with chest pain and normal coronary arteries evidenced by coronary angiography and CSF were included in this randomized, double-blind, placebo-controlled trial. CSF patterns were evaluated by the corrected TIMI frame count. Patients were randomly assigned at 1∶1 ratio to diltiazem sustained-release capsules treatment group (Dil, 90 mg twice daily) or placebo control group. Holter, liver and kidney function, treadmill exercise test, coronary angiography and left ventricular angiography were measured at baseline and after 6 months. The incidence of cardiovascular events (re-admission or progress in coronary heart disease, myocardial infarction, malignant arrhythmia or cardiac death) was evaluated during the 6 months follow up.ResultsThirty-nine patients in control and 40 patients in Dil group completed the 6 months follow-up. There was no medication induced drug withdraw during follow up. Left ventricular ejection fraction was similar between the 2 groups at baseline and during follow up. Heart rate was significantly lower in Dil group than in control group and there was no symptomatic bradycardia and II and III degree atrioventricular conduction block in both groups. Significant improvement was observed in the onset of chest pain, treadmill exercise test and coronary blood flow in Dil group while these parameters remained unchanged in control group at the end of 6 months follow up. The incidence of cardiovascular events was similar between the two groups.ConclusionDiltiazem slow-release capsules improved coronary blood flow and alleviated angina in patients with CSF.Trial RegistrationChinese Clinical Trial Registry ChiCTR-TCC-11001864

Effect of eye acupuncture on plasma PGF2α in patients of primary dysmenorrhea

ObjectiveTo observe the clinical curative effect of eye acupuncture therapy on primary dysmenorrhea and the effect on content of prostaglandin F2α (PGF2α) in peripheral blood of menstrual periods. MethodsOne hundred and ten cases of primary dysmenorrhea were randomly divided into an eye acupuncture group (60 cases) and a medication group (50 cases). In the eye acupuncture group, lower-jiao area, liver area, kidney area, heart area and spleen area, etc. were selected according to syndrome differentiation, and the eye acupuncture therapy was applied. In the medication group, 300 mg Ibuprofen sustained release capsule was orally administrated 1–2 days before menstrual onset or when the symptoms appeared, once every 12 hours, for 3–5 days totally, 3 menstrual periods constituting one therapeutic course. The content of PGF2α in peripheral blood, and the curative effects and recurrence 3 and 6 months after treatment were observed. ResultsThree months after treatment, the cured rate was 55.0% (33/60) and the total effective rate was 95.0% (57/60) in the eye acupuncture group, which were superior to those of 34.0% (17/50) and 82.0% (41/50) in the medication group (both P<0.05). According to the following-up after 6 menstrual cycles, the recurrence rate of 9.1% (3/33) in the acupuncture group was significantly lower than that of 35.3% (6/11) in medication group. The contents of PGF2α in peripheral blood of menstrual periods were reduced after treatment in the two groups (both P<0.01). ConclusionThe curative effect of eye acupuncture on primary dysmenorrhea is significant, with the level of PGF2α in peripheral blood of menstrual periods reduced.

Determination of sinomenine sustained-release capsules in healthy Chinese volunteers by liquid chromatography–tandem mass spectrometry

A sensitive and selective liquid chromatographic tandem mass spectrometric method was developed and validated for the determination of sinomenine in human plasma. Plasma samples were precipitated using methanol with metronidazole as internal standard. Separation was carried out on an Inertsil ODS-3 column using a mixture of 0.2% ammonium acetate solution (A) and methanol (B) as the mobile phase with linear gradient elution as follows: 0min (50%B)→1.5min (80%B)→4.5min (80%B)→4.6min (50%B)→6.0min (50%B). All mass data were obtained in the positive ion mode, and the fragmentation transitions for the selective multiple reaction monitoring were m/z 330→181 and 172→128 for sinomenine and metronidazole, respectively. The method was fully validated to be accurate and precise with a linear range of 0.5–500ng/mL and applied to a single- and multiple-dose pharmacokinetics study of sustained-release capsules of sinomenine hydrochloride in 20 healthy Chinese volunteers. After oral administration of a single 60-mg dose, the Tmax, Cmax, AUC0–96 and t1/2 were 7.9±2.0h, 123±22ng/mL, 3032±682ngh/mL and 13.4±1.6h, respectively. After oral administration of the 60mg capsules twice-daily for 7 consecutive days, these parameters were 4.4±3.6h, 279±69ng/mL, 7333±2096ngh/mL and 15.1±1.3h, respectively. The AUC and Cmax values after multiple-dose treatment were significantly higher than those after a single-dose treatment (P<0.01), with an accumulation factor of 2.49±0.77.

Erratum

A rapid, sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of propiverine hydrochloride (CAS 54556-98-8) in human plasma using cetirizine di-hydrochloride as internal standard (IS, CAS 8388-51-0). Following liquid-liquid extraction with ethyl acetate, the separation was performed on a reverse phase C18 column with a mobile phase consisted of methanol-ammonium acetate (pH 4.0; 10 mM) (70:30, v/v). The detection was performed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 368.3 → 116.1 for propiverine and m/z 389.2 → 201.0 for the IS. The calibration curve fitted well over the concentration range of 0.2–200 ng/mL (all the concentration data in this study are related to salt (propiverine hydrochloride)). The limit of detection (LOD) and lower limit of quantification (LLOQ) in human plasma were 0.05 and 0.2 ng/mL, respectively. The method was proved to be rapid, sensitive, specific, accurate and reproducible and has been successfully applied to a pharmacokinetic study of propiverine hydrochloride sustained release capsules (the 30 mg dose in this study is related to 30 mg of salt (propiverine hydrochloride)). The major pharmacokinetic parameters in healthy Chinese volunteers are given for the first time and the sustained release characteristics of the sustained release formulation are evaluated.

Preparation and in vitro/in vivo evaluation of sustained-release venlafaxine hydrochloride pellets

The objective of this study was to prepare different venlafaxine hydrochloride sustained-release products and to elucidate the influence of composition of the coating film on the in vitro drug release profiles and in vivo pharmacokinetics. Pellets were prepared by a standardized process of extrusion/spheronization. A selected fraction size (0.8–1.0mm diameter) of pellets of each formulation was coated with Eudragit® NE30D or ethylcellulose (10cps). Many efforts have been made to tailor drug release rate by choosing different coating materials, different percent of pore forming components and coating weight variation to achieve a desired sustained-release effect. The dissolution studies were performed and data were analyzed in terms of cumulative release as a function of time. The influence on the release of venlafaxine from sustained-release capsules was observed in dissolution media of different pH and gradient pH. Scanning electron microscope (SEM) micrographs revealed morphological changes of the pellet coating surface which were related to in vitro drug release profiles. The relative bioavailability for Formulation 1 and Formulation 2 was evaluated in six healthy beagle dogs after oral administration in a fast state using sustained-release capsules (Effexor® XR) as a reference. The results suggested that Formulation 1 and Formulation 2 both had better bioavailability compared with Effexor® XR. It could be found that there existed quite difference in the in vivo release and oral absorption performances, despite the similar in vitro drug release behavior for the two formulations. It might be attributable to complex in vivo environment and then variation in the release behavior. Thus differences in the film micro-structure and surface roughness caused by aqueous dispersion and organic solvent coating techniques strongly influence the in vivo release and oral absorption performances.

Evaluation of Ursodeoxycholic Acid Bioavailability from Immediate- and Sustained-release Preparations Using Gas Chromatography-Mass Spectrometry and High-performance Liquid Chromatography

An improved procedure is presented for the determination of ursodeoxycholic acid (CAS 128-13-2, UDCA) in human plasma and bile after oral administration of UDCA-containing dosage forms. The plasma samples after solid-phase extraction with silica-based C18- and strong anion exchange cartridges were assayed by gas chromatography-mass spectrometry (GC-MS) using selected-ion monitoring. The hexafluoroisopropyl trifluoroacetate ester derivative of UDCA was selected for GC analysis since it is easily and rapidly prepared by a one-step reaction. Biliary UDCA levels were determined by a rapid and simple high-performance liquid chromatographic (HPLC) method with on-line sample purification. This analytical protocol was used to investigate the pharmacokinetic of a new sustained-release capsule of UDCA in comparison with a reference immediate-release preparation after single oral administration. Statistical evaluation of the area under the plasma concentration-time curves indicated that two formulations are equivalent with regard to the amount of drug absorbed. However, pharmacokinetic data showed that with the sustained-release preparation a significantly delayed mean peak plasma level was reached compared with the reference preparation. Moreover, the immediate- and extended-release capsules were found to achieve a comparable degree of biliary enrichment with UDCA.

Determination of propiverine hydrochloride in human plasma by high performance liquid chromatographytandem mass spectrometry: application to the pharmacokinetic study of a sustained release formulation

A rapid, sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of propiverine hydrochloride (CAS 54556-98-8) in human plasma using cetirizine di-hydrochloride as internal standard (IS, CAS 8388-51-0). Following liquid-liquid extraction with ethyl acetate, the separation was performed on a reverse phase C18 column with a mobile phase consisted of methanol-ammonium acetate (pH 4.0; 10 mM) (70:30, v/v). The detection was performed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 368.3 --> 116.1 for propiverine and m/z 389.2 --> 201.0 for the IS. The calibration curve fitted well over the concentration range of 0.2-200 ng/mL (all the concentration data in this study are related to salt (propiverine hydrochloride)). The limit of detection (LOD) and lower limit of quantification (LLOQ) in human plasma were 0.05 and 0.2 ng/mL, respectively. The method was proved to be rapid, sensitive, specific, accurate and reproducible and has been successfully applied to a pharmacokinetic study of propiverine hydrochloride sustained release capsules (the 30 mg dose in this study is related to 30 mg of salt (propiverine hydrochloride)). The major pharmacokinetic parameters in healthy Chinese volunteers are given for the first time and the sustained release characteristics of the sustained release formulation are evaluated. [corrected].

Fatty Acid and Water-Soluble Polymer-Based Controlled Release Drug Delivery System

Sustained release capsule formulations based on three components, drug, water-soluble polymer, and water-insoluble fatty acid, were developed. Theophylline, acetaminophen, and glipizide, representing a wide spectrum of aqueous solubility, were used as model drugs. Povidone and hydroxypropyl cellulose were selected as water-soluble polymers. Stearic acid and lauric acid were selected as water-insoluble fatty acids. Fatty acid, polymer, and drug mixture was filled into size #0 gelatin capsules and heated for 2 h at 50 °C. The drug particles were trapped into molten fatty acid and released at a controlled rate through pores created by the water-soluble polymer when capsules were exposed to an aqueous dissolution medium. Manipulation of the formulation components enabled release rates of glipizide and theophylline capsules to be similar to commercial Glucotrol XL tablets and Theo-24 capsules, respectively. The capsules also exhibited satisfactory dissolution stability after exposure to 30 °C/60% relative humidity (RH) in open Petri dishes and to 40 °C/75% RH in closed high-density polyethylene bottles. A computational fluid dynamic-based model was developed to quantitatively describe the drug transport in the capsule matrix and the drug release process. The simulation results showed a diffusion-controlled release mechanism from these capsules.

Naloxone Hydrochloride Sr Gastro-Resistant Sustained Release Capsules, (Nalcol™) as a Treatment for Functional Constipation: A Randomised, Double Blind Controlled Trial in Secondary Care – Preliminary Results

Naloxone Hydrochloride Sr Gastro-Resistant Sustained Release Capsules, (Nalcol™) as a Treatment for Functional Constipation: A Randomised, Double Blind Controlled Trial in Secondary Care – Preliminary Results

Oral sustained-release cisplatin capsule.

An oral sustained-release cisplatin preparation was prepared by combining microporous water-insoluble pharmaceutical polymer, ethylcellulose, a membrane and a gel-forming polymer, poly(acrylic) acid (Carbopol). As cisplatin is an extremely hydrophilic and small compound, it was difficult to control the release rate solely by the micropores on the ethylcellulose capsule. To retain cisplatin within the capsule, gel-forming polymer was formulated inside the capsule. The release rate of cisplatin was dependent both on the number of micropores of the capsule and the formulated amount of Carbopol. The number of micropores ranged from 20 and 30 to 60, and the formulated amount of Carbopol varied from 15 to 100 mg. In-vitro release experiments suggested that the release rate decreased as the formulated amount of Carbopol increased when the pore number was 60 and 30. However, when pore number was decreased to 20, the effect of the amount of Carbopol was not clearly observed. In the in-vivo study using rabbits, the sustained-release cisplatin capsule was evaluated in comparison with solution after oral administration of 20 mg drug. With the pore number of 60, Cmax was 0.46 +/- 0.02 microgram mL-1 at 4 h and thereafter serum concentrations declined rapidly. When the pore number was 30, serum cisplatin level-time profiles showed long-acting patterns and AUC was reversely correlated with the formulated amount of Carbopol. Cmax and tmax were 0.41 +/- 0.02 microgram mL-1 and 3.33 +/- 0.88 h, respectively and 0.23 +/- 0.01 microgram mL-1 was obtained at 24 h after oral administration of capsule having 30 pores and 15 mg of Carbopol. We conclude that the possibility of developing an oral sustained-release cisplatin preparation is feasible.

Pharmacokinetics and bioequivalence of methylphenidate hydrochloride sustained-release micropellet capsules in rabbits

Objective: To study the pharmacokinetics and bioequivalence of self-prepared methylphenidate hydrochloride(MPH) sustained-release micropellet capsules.Methods: Eight rabbits were given a single oral dose of 18 mg of MPH sustained-release micropellet capsules(test preparation) and MPH controlled-release tablets on the market(reference preparation) in a crossover study.LC/MS/MS method was employed to determine the plasma concentrations of MPH before and 0.5,1,2,3,4,6,8,10,12,24 and 32 h after administration of the medicine.The pharmacokinetic parameters were calculated and statistically analyzed.Results: The detection limit of MPH was 0.06 ng/ml.The plasma concentration curves of both the sustained-release micropellet capsules and the controlled-release tablets had two peaks.The main pharmacokinetic parameters of test preparation were as follows:tmax1=(1.02±0.04) h,tmax2=(5.98±0.03) h,cmax1=(0.82±0.22) ng/ml,cmax2=(1.54±0.33) ng/ml and those of reference preparation were as follows:tmax1=(0.50±0.02) h,tmax2=(3.96±0.03) h,cmax1=(0.45±0.12) ng/ml,cmax2=(1.25±0.29) ng/ml,respectively.The cmax and tmax of both peaks of the test preparation were higher or longer than those of the reference preparation.Conclusion: Compared with the controlled release tablets,the self-prepared MPH sustained-release micropellet capsules have better bioavailability.

Clinical observation on 36 cases of acute gouty arthritis treated with Tongfengxiao decoction

Objective To observe the effect of self mading Tongfengxiao decoction in treatment of acute gouty arthritis. Methods 69 patients were randomly divided into two groups. In the control group,33 patients were given diclofenac sodium sustained-release capsules and allopurinol treatment;In treatment group ,36 patients were given to the self mading Tongfengxiao decoction in addition to the western medicine received by the control group. The two groups were all treated for 14 days. Results The total effective rate was 94.4% for treatment group and 87.8% for control group respectively. Therefore, the difference of treatment effect between twp groups was significant ( P ＜0. 05 ) ;Also, the treatment group performed better than control group in term of reducing serum uric acid( P ＜ 0. 05).Conclusion The treatment of Tongfengxiao decoction combined western medicine for acute gouty arthritis had a good synergistic effect, and could reduce serum uric acid and improve clinical symptoms. Key words: Acute gouty arthritis; Tongfengxiao Decoction; Diclofenac sodium sustained-release capsules; Allopurinol

Quality evaluation of Ketoprofen Solid Dosage Forms Available in the Pharma-Market of Bangladesh

Problem statement: Ketoprofen, a widely used analgesic and anti-inflammatory drug, was available in two types of solid dosage forms in the pharma-market of Bangladesh: enteric-coated tablet and capsule of sustained-release pattern. Seven brands of ketoprofen enteric-coated tablets and four brands of ketoprofen sustained release capsules were studied for their in-vitro release behavior as well as potency status. Approach: The studies were carried out to compare with standard sample of ketoprofen sustained-release pellets and that of ketoprofen powder. To determine the release pattern of the preparations, disintegration study and dissolution tests were performed as per the method described in standard pharmacopeial compendia (British Pharmacopoeia or BP and United State Pharmacopoeia or USP respectively). The potency of the samples were determined by the UV spectroscopic method as described in BP. Results: Out of seven samples of tablets, two brands (KT-03 and KT-07) were found noncompliant in respect of disintegration test in acid stage whereas rest of the brands complied with BP specification in buffer stage at pH 6.8. The dissolution study of ketoprofen tablets were carried out in both acid and buffer stages and all the samples satisfied with USP specification in both stages. All of the brands of ketoprofen capsule also complied with the USP specification. Two brands (KT-03 and KT-07) of tablets were found non-compliant whereas rest brands of tablets and all brands of capsules exerted compliance in respect of potency. Conclusion: This study will provide a basis for further in-vivo bioavailability studies of these brands to draw a more conclusive remark regarding quality status of these samples.

Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

In vitro and in vivo evaluation of levofloxacin sustained-release capsules

Objective: To reduce the frequency of administration and improve patient compliance, novel levofloxacin sustained-release capsules with suitable in vitro release profiles and good bioavailability were developed. Materials and methods: A fluidized bed was used to prepare levofloxacin pellets by spraying the drug solution onto blank pellets. Then the pellets were coated with either Surelease water dispersion or Eudragit® NE30D water dispersion to achieve sustained-release characteristics. The mixed pellets containing 15% of the uncoated pellets and 85% of the coated pellets were filled into the hard gelatin capsules. In vitro release test was performed with the capsules. A single-dose pharmacokinetic study of the capsules was carried out in beagle dogs. Results: Although Eudragit® NE30D-coated pellets and Surelease-coated pellets showed similar sustained-release profiles in vitro, their in vivo pharmacokinetic characteristics exhibited significant difference. Unsuccessful in vivo–in vitro correlation was shown in Eudragit® NE30D-coated pellets with a relative bioavailability of only 41.5%, whereas Surelease-coated pellets achieved best sustained-release feature both in vitro and in vivo with a relative bioavailability of 103.0%. Conclusion: Statistical analysis indicated that the capsules containing Surelease-coated pellets had a satisfactory sustained-release behavior and a desired pharmacokinetic property.