Study of the quantitative factors influence on pharmaco-technological properties of powder masses and tablets with plant extracts and essential oil

The available range of phytopreparations for topical use in the oral cavity does not fully meet the needs of patients as mainly medicinal plant raw materials and tinctures of domestic production represent it. Therefore, we developed a pharmaceutical composition in the form of tablets based on dry extracts herb of Geranium sanguineum L., Geranium sibiricum L. and essential oil of Salvia sclare. To optimize the composition of the tablets it is necessary to study and select the necessary excipients and their quantities, which was the purpose of the work. In order to study the influence of 10 quantitative factors on the properties of powder masses and the main quality indicators of tablets with plant extracts and essential oil, the method of random balance was used. The obtained powder mixtures and tablets based on them were subjected to the determination of the following pharmaco-technological parameters: bulk density, tapped density, flowability, the angle of repose, the uniformity of weight, tablet hardness testing, the friability test, disintegration time, desirability function. The pharmaco-technological index of bulk density improves with an increase in the amount of Pregelatinized Starch, Mannitol 60, Emcompress, as well as a decrease in the amount of Neusilin UFL2 and Neusilin US2. Regarding the tapped density, Neusilin US2 significantly affects it, with the increase of which this indicator decreases. With the introduction of more Neusilin US2, Mannitol 60, Pregelatinized Starch, Ludipress, Emcompress and Magnesium Stearate, the value of the angle of repose is improved. The average mass has the greatest influence on fluidity, at its decrease this indicator improves. The same happens with the introduction of Neusilin UFL2, Neusilin US2, Pregelatinized Starch and Magnesium Stearate. The uniformity of weight of all series of tablets fluctuates within ± 5%, and friability to 1%, which meets the requirements of the State Pharmacopoeia of Ukraine. Also, despite the results obtained, all series of tablets were very strong, with the lowest tablet hardness testing – 159 N. The disintegration of the tablets varies within 6 minutes. After evaluating the results of the scattering diagrams of all pharmaco-technological parameters as well as the desirability function, Neusilin US2, МCC 102, Sodium croscarmellose, Mannitol 60 and Magnesium Stearate were selected for further research. The average weight of tablets should be increased to 0.55 g.

Liquisolid Tablets Formulation of Atorvastatin Calcium Using Polyethylene Glycol 400 as Solvent and Some Carrier Materials

The dissolution of atorvastatin calcium need to be improved since included BCS Class II drugs with low solubility and high permeability, meaning that the dissolution affects the bioavailability of drugs. This research aimed to develop a formulation of a liquisolid tablet using PEG 400 as a solvent and some carrier materials in various compositions to increase the dissolution of atorvastatin calcium. Different formulations of liquisolid tablets were conducted using different quantities of carrier and coating material for adsorbing liquid solvent to produce a free-flowing and compressible powder. Avicel PH 101, Avicel PH 102, Neusilin US2 were employed as the carrier and Aerosil 200 as the coating material. A disintegrant and lubricant were then added to the formed liquisolid system and compressed into tablets by the direct compressing method. The liquisolid tablets were characterized for their tableting properties and possible drug-excipient interaction by XRD and FTIR analysis. The tableting characteristics of atorvastatin calcium liquisolid tablets were within the acceptable limits criteria. The dissolution of AA4 and NA1 liquisolid tablets was higher compared to marketed tablets. Based on the XRD and FTIR analysis, no interactions between drug and excipient.

Diseño y desarrollo de un sistema de entrega de fármaco autoemulsificable líquido de ibuprofeno incorporado por el método de adsorción por portador en una forma farmacéutica sólida (comprimidos)

El ibuprofeno es uno de los fármacos más utilizados e indicado para terapias antiinflamatorias, dolor, entre otras patologías. Sin embargo, este fármaco presenta una baja y errática biodisponibilidad, debido a la pobre solubilidad acuosa intrínseca del mismo, por lo cual esta categorizado como clase II en el sistema de clasificación biofarmacéutica. El objetivo de este trabajo fue desarrollar, diseñar y evaluar un sistema de entrega de fármaco autoemulsificable (SEDDS) para mejorar la solubilidad y velocidad de disolución de ibuprofeno.Aceites, cosolventes, tensioactivos y portadores porosos fueron evaluados por su capacidad de mejorar la solubilidad del ibuprofeno, habilidad de autoemulsificación, robustez en diferentes pH y capacidad de adsorción. El aceite de coco, Tween 80 y propilenglicol lograron un aumento significativo de la solubilidad acuosa del ibuprofeno en un tiempo de autoemulsificación menor a 2 minutos. Neusilin US2® fue seleccionado como portador, dando como resultado un pequeño granulo de excelente fluidez, que permitió obtener comprimidos que cumplieron satisfactoriamente las pruebas de control de acuerdo con las especificaciones establecidas. Los SEDDS líquidos y sólidos son una alternativa de formulación ventajosa y prometedora para mejorar la solubilidad de fármacos pobremente solubles de acuerdo con el sistema de clasificación biofarmacéutica, a través de sus propiedades de solubilización.

THE THE METHOD OF RANDOM BALANCE FOR STUDYING THE INFLUENCE OF EXCIPIENTSʼ QUANTITIES ON TECHNOLOGICAL PARAMETERS OF METFORMIN ORODISPERSIBLE TABLETS

Objective: The present investigation was undertaken with an objective of analyzing the influence of excipientsʼ amount on the technological parameters of metformin orodispersible tablets using the method of random balance. Methods: The tablets were prepared by using direct compression method. The formulations were designed according to the method of random balance. The technological parameters of metformin orodispersible tablets have been studied as a function of quantitative factors: crospovidone (Polyplasdone XL-10®), magnesium aluminometasilicate (Neusilin US2®), microcrystalline cellulose (MCC Sanaq® burst), lactose monohydrate, magnesium stearate (Tablube® MgSt micronized vegetable) and talc. Results: The flowability results were ranging from excellent to good according to the quantities of Neusilin US2® and Polyplasdone XL-10® crospovidone, which used. Results of bulk density and tapped density of the powder mixtures for pressing depended from the quantities of Neusilin US2® and talc. The obtained tablets had uniform weight from 0.93 to 2.30 %. The increase in the amount of Polyplasdone XL-10® crospovidone and the decrease in the amount of talk improved the uniformity of tablets’ weights. All of the prepared tablets showed acceptable hardness and friability which were improved with decrease in the amount of MCC Sanaq®burst and increase in the amount of Neusilin US2®. The rapid disintegration and wetting time for all formulations of tablets were obtained by using the Polyplasdone XL-10® crospovidone and MCC Sanaq®burst. Conclusion: Oral disintegrating tablets of metformin were successfully prepared by direct compression method. The random balance method enabled us to identify the most significant quantitative factors and stabilize them at optimal values.

Calcium Alginate-Neusilin US2 Nanocomposite Microbeads for Oral Sustained Drug Delivery of Poor Water Soluble Drug Aceclofenac Sodium

The aim of the present study was to formulate and investigate the calcium alginate- (CA-) Neusilin US2 nanocomposite microbeads containing preconcentrate of aceclofenac sodium (ACF-Na) liquid microemulsion (L-ME) for enhancement of oral bioavailability. The preconcentrate L-ME is prepared by using Labrafac PG, Labrasol, and Span 80 as oil, surfactant, and cosurfactant, respectively. The solid CA nanocomposite microbeads of L-ME prepared by microemulsification internal gelation technique using sodium alginate (SA) gelling agent, Neusilin US2 as adsorbent, and calcium chloride as crosslinking agent. L-ME has good thermodynamic stability; globule size was found to be 32.4 nm with polydispersity index 0.219 and −6.32 mV zeta potential. No significant interactions of excipients, drug in the formulations observed by FT-IR, DSC and XPRD. The concentration of SA and Neusilin US2 influences the flow properties, mean particle size, mechanical strength, drug entrapment efficiency, and percentage of drug release. All the formulations show minimum drug release in simulated gastric fluid (SGF) pH 1.2 for initial 2 h, maximum drug release in pH 6.8 phosphate buffer solution (PBS) at 6 h, followed by sustaining in simulated intestinal fluid (SIF) of pH 7.4 up to 12 h. The interaction of SA with Neusilin US2 creates a thick thixotropic gel network structure which acts as barrier to control the release of drug in the alkaline pH environment. Neusilin US2 is a novel filler used to convert L-ME into solid nanocomposite microbeads to enhance dissolution rate of poor water soluble drugs sustaining the drug release for prolonged period of time.