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Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride.

ABSTRACT: Ranitidine HCl, a selective, competitive histamine H2-receptor antagonist with a short biological half-life, low bioavailability and narrow absorption window, is an ideal candidate for gastro-retentive drug delivery system (GRDDS). Controlled release with an optimum retentive formulation in the upper stomach would be an ideal formulation for this drug. The aim of the present study was therefore to develop, formulate and optimize floating, bioadhesive, and swellable matrix tablets of ranitidine HCl. The matrix tablets were prepared using a combination of hydroxypropyl methylcellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC) as release retarding polymers, sodium bicarbonate (NaHCO3) as gas generating agent and microcrystalline cellulose (MCC) as direct compression diluent. Central composite design (CCD) was used to optimize the formulation and a total of thirteen formulations were prepared. Concentration of HPMC/NaCMC (3:1) (X1) and NaHCO3 (X2) were selected as independent variables; and floating lag time (Y1), bioadhesive strength (Y2), swelling index at 12 h (Y3), cumulative drug release at 1 h (Y4), time to 50% drug release (t50%) (Y5) and cumulative drug release at 12 h (Y6) were taken as the response variables. The optimized batch showed floating lag time of 5.09 sec, bioadhesive strength of 29.69 g, swelling index of 315.04% at 12 h, t50% of 3.86 h and drug release of 24.21% and 93.65% at 1h and 12 h, respectively, with anomalous release mechanism. The results indicate that sustained release matrix tablet of ranitidine HCl with combined floating, bioadhesive and swelling gastro-retentive properties can be considered as a strategy to overcome the low bioavailability and in vivo variation associated with the conventional ranitidine HCl tablet.

SUBMITTER: Nigusse B

PROVIDER: S-EPMC8232414 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. METHODS:Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20?mg/day; participants were titrated in 10-20?mg/day increments weekly based on efficacy and tolerability (maximum dose, 60?mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60?mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. RESULTS:Mean MPH ERCT daily dose increased weekly from 29.4?mg/day after the first dose adjustment at week 1 (n?=?90) to 42.8?mg/day after the final adjustment at week 5 (n?=?86). Final optimized MPH ERCT dose ranged from 20 to 60?mg/day. Mean final optimized MPH ERCT dose ranged from 40.0?mg/day in 6-8 year-old participants to 44.8?mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60?mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20?mg/day (42.4 [1.34] vs. 35.1 [2.55]; p?=?0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. CONCLUSIONS:Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Project description:BackgroundBerberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability.ObjectiveIn this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR.MethodsThree-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs.ResultsBased on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC50 = 56 μM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC50 > 150 μM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations.ConclusionsA new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.

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Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride.

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