Larvicidal activity of granulated pharmaceutical products using Indonesian holy basil leaf extract

<em>Ocimum sanctum</em> Linn, known as holy basil, is a larvicide, which is relatively safe compared to synthetic insecticides. This study investigates the larvicidal activity of a granule formulation of Indonesian holy basil leaf extract against third larval instar of <em>Aedes aegypti</em>. The extract of holy basil leaves was obtained by a maceration process with 96% ethanol. The granule was formulated with various concentrations of holy basil leaf extract, including F1 (2000 ppm), F2 (4000 ppm), and F3 (6000 ppm). The extract contained terpenoid, alkaloid, saponin, flavonoid, and polyphenol compounds. The extract granules had a moisture content of 3.01%, flowability of 1.51 seconds, and dispersion time of 1.09 seconds. The mortality rates of mosquitos treated with the different formulation groups were significantly different from positive control with values of 25.33% (F1), 50.67% (F2), and 90.67% (F3). In conclusion, the granulated formulation of holy basil leaf extract has a larvicidal LC₅₀ of 4405.803 ppm and LC₉₀ of 6080.714 ppm. Therefore, a granulated pharmaceutical product derived from holy basil leaf extract could be developed as a potent larvicide to control dengue fever.

Efektivitas Larvasida Granul Ekstrak Etanol Daun Pisang Nangka (Musa x paradisiaca L.) terhadap Larva Nyamuk Aedes aegypti

Musa x paradisiaca L. leaves are known to contain phenols, flavonoids, saponins, tannins, and other compounds that can be used as larvicides. This study aims to determine the effect of Musa x paradisiaca L leaves’ ethanol extract granules on the mortality of Aedes aegypti larvae. The Research was experimental in two stages of effectiveness testing, that are extract and granule formula effectiveness test. Data were analyzed using the Kruskal-Wallis test and the Mann-Whitney test. The extraction method used was maceration using 96% ethanol. The concentration of the extract dosage used were 0.2; 0.5; 1; 2; and 4%, with control (+) temephos and control (-). Repetitions were carried out 3 times with a sample total of 675 larvae. Observations were made for 12 and 24 hours. Preparation of granules using 2 formulas, formula 1 granules without extract and formula 2 granules with the extract. To fulfill the granule formulation criteria, the preparation was evaluated. The results showed that the concentration of 4% extract was the most effective at 98.7%, as stated by the Kruskal-Wallis test result,p-value <0.05, which means that there was an effect on the effectiveness of larvicide. The percentage of mortality of larvae given formula 2 is 100% and based on the Mann-Whitney test with value p<0.05, there is a difference between granule 1 and 2 formula. Criteria of granule including moisture content (1.72 %), angle of rest 240, flow velocity (50 gr/sec), and dispersion time (2.25 minutes). The granular formula of Musa x paradisiaca L leaves can make the application easier and hopefully can be used as effectively as synthetic larvicide in the community.

Analysis of the Effect of Body Lossion of Rattus Norvegicus on Granulation Formulation of Chitosan Waste Shell of Placuna Placenta

Weight loss Rattus norvegicus wistar strain can be done by a variety of chemical and traditional medicine. One of the traditional medicines used for weight loss is to use Placuna Placenta chitosan. The purpose of this study was to determine the optimal concentration of Placuna Placuna Placenta granules as a weight loss agent for Rattus norvegicus. This study was an experimental study with 5 concentrations of 5%, 7.5% and 10% Placuna Placuna Placenta chitosan observed for 30 days. The positive control used weight loss drugs in the market, while the negative control used granule formulation without the addition of Placuna Placuna Placenta chitosan. The experimental research design posttest only control group design, treatment or intervention in the experimental group by comparing groups. Comparisons or differences were analyzed statistical tests using the ANOVA test. The optimal concentration of chitosan granule formulation of Placuna Placuna Placenta as a weight loss for Rattus norvegicus wistar strain was 10%.

Mesalazine granule formulation improves clinical data in Crohn's disease compared with tablet formulation

The efficacy of sustained-release preparations of mesalazine as a remission maintenance treatment for Crohn's disease remains to be established. We aimed to examine the changes in compliance rate and clinical data 2 years after switching from mesalazine tablet to granule formulation at our facility among patients with Crohn's disease in remission. We investigated the rate of continuous treatment of mesalazine granules and examined the changes in Crohn’s Disease Activity Index (CDAI) and serum C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels 2 years after the switch. Compliance rate (continuous treatment vs. additional treatment) and continuous treatment rate [good (rate of ≥ 70%) vs. poor (rate < 70%)] were investigated. Of 46 patients, 12 (27.3%) received additional treatment and 32 (72.7%) did not require additional treatment in 2 years. No significant change in CDAI after switching to granule modification was noted in 32 patients in the continuous treatment group. Nevertheless, clinical remission was maintained for 2 years, and serum CRP levels decreased significantly (P = 0.023) and Hb levels increased significantly (P = 0.002). No change in the compliance rate was found. Our results suggest that mesalazine granule formulation may have a remission maintenance effect that is superior to that of mesalazine tablets.

CTNI-09. A PHASE I HEALTHY VOLUNTEER STUDY ON THE RELATIVE BIOAVAILABILITY AND FOOD EFFECT OF CAPSULE AND GRANULE FORMULATIONS OF SELUMETINIB

Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective allosteric MEK 1/2 inhibitor approved by the FDA as a capsule formulation for treatment of pediatric patients ≥ 2 years old with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. A new granule formulation is being developed to support dose flexibility and for patients unable to swallow capsules. This Phase I, open-label, single-center, randomized crossover pharmacokinetics study (NCT03649165) investigated the new granule versus capsule formulation in both fasted and fed (low-fat) states. Twenty-four healthy adult male volunteers were randomized to receive single-dose selumetinib in one of four treatment sequences: 25 mg granule (fasted); 50 mg capsule (fasted); 25 mg granule (fed); and 50 mg capsule (fed). Primary endpoint: to compare pharmacokinetics of the formulations in fasted state. Secondary endpoints: pharmacokinetics of the formulations in fasted versus fed states, granule palatability, safety and tolerability. In fasted state, a slight delay in absorption of selumetinib by ~0.60 h, with geometric mean ratios (90% CI) of 0.65 (0.58, 0.74) for Cmax/dose and 0.87 (0.81, 0.92) for AUC/dose, was detected when administered as granule versus capsule. For granule in fed versus fasted states, geometric mean Cmax and AUC ratios (90% CI) were 0.61 (0.51, 0.72) and 0.97 (0.91, 1.02). For capsule in fed versus fasted states, geometric mean Cmax and AUC ratios (90% CI) were 0.40 (0.33, 0.48) and 0.62 (0.55, 0.70). Granule palatability was acceptable; volunteers indicated they would take it again. Selumetinib was well-tolerated; for both formulations, few adverse events of mild intensity were reported; dry eyes (fasted) versus dry eyes and rhinorrhea (fed) were most frequent. This was the first study to test the granule formulation in humans; results indicate the granule formulation has similar AUC to the capsule formulation and minimal food effect, supporting planned clinical trials in pediatric patients.

A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles

Purpose The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids. Methods Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active ingredient and drug product with liquid dosing vehicles and soft foods commonly ingested by infants, pre-school- and school children. Drug solubility and stability experiments in the different vehicle types and, drug release/dissolution experiments mimicking age-related pediatric gastric conditions after administering the hydrocortisone granules together with the dosing vehicles and after different exposure/mixing times were performed. Results In the simulated dosing scenarios applied in dissolution experiments, in vitro dissolution in gastric conditions was rapid and complete. Results of the chemical compatibility/stability studies indicated that mixing with the different dosing vehicles studied should not be an issue regarding drug degradation products. Conclusions A novel in vitro approach ensuring a proper risk assessment of the use of dosing vehicles in the administration of pediatric dosage forms was established and applied to a novel pediatric hydrocortisone drug product. The studied dosing vehicles were shown to not alter performance of the drug product and are thus considered suitable for administration with hydrocortisone granules.

Optimization of Formula Granule of Lempuyang Gajah (Zingiber zerumbet (L) J.E.Smith) Rhizome Purified Extract as a Larvicide

Lempuyang gajah rhizome (Zingiber zerumbet (L) Smith is considered potential as larvicidal. A previous study has shown that the purified extract of Z. zerumbet rhizome was toxic against Adese aegypti larvae. The aim of the study it to formulate a purified extract of Z. zerumbet (L) Smith in granule preparations by combining Sodium starch glycolate, PVP K-30 and tween 80. The granule formulation was optimized by the Simplex Lattice Design (SLD) method with using Design expert program 7.1.5. The results showed that the interaction of the three components can increase the flow rate index, the angle of repose, and reduce absorption. The optimum formula obtained was Sodium starch glycolate 2%, PVP K-30 2%, and Tween 80 5%. The analysis of one sample t-test shows that there is no significant difference between the predicted parameter values and the experimental results of the flow rate index and angle of repose, while the absorption response is significantly different. The optimum formula for granules has larvicidal activity with 100% larval death during 12-hour treatment.