Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance

Lukášová, Ivana; Muselík, Jan; Franc, Aleš; Goněc, Roman; Mika, Filip; Vetchý, David

doi:10.1016/j.ejps.2017.09.017

Cited by 9 publications

(4 citation statements)

References 21 publications

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“…The drug content homogeneity of active pharmaceutical ingredients (APIs) in the dosage form is one of the most critical quality attributes, especially in low-dose products [62,63]. The content homogeneity of DUT in NSCs and physical mixture-07 was assessed as NSCs contained low dose of DUT [DUT:NSC = 1:30 (w/w)].…”

Section: Characterization Of Nsc and Nsc Tablet 331 Drug Content Hmentioning

confidence: 99%

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

2021

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This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique. NSC microemulsion formation was confirmed using a ternary phase diagram, while the presence of DUT and lipid entrapment in NSC was confirmed using scanning electron microscopy. Differential scanning calorimetry and X-ray diffraction revealed the amorphous properties of NSC. The prepared all NSC had excellent flowability and enhanced DUT solubility but showed no significant difference in drug content homogeneity. An increase in the lipid content of NSC led to an increase in the DUT solubility. Further the NSC were formulated as tablets using D-α tocopheryl polyethylene glycol 1000 succinate, glyceryl caprylate/caprate, and Neusilin®. The NSC tablets showed a high dissolution rate of 99.6% at 30 min. Furthermore, NSC stored for 4 weeks at 60 °C was stable during dissolution testing. Pharmacokinetic studies performed in beagle dogs revealed enhanced DUT bioavailability when administered as NSC tablets. NSC can be used as a platform to develop methods to overcome the technical and commercial limitations of lipid-based preparations of poorly soluble drugs.

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Section: Characterization Of Nsc and Nsc Tablet 331 Drug Content Hmentioning

confidence: 99%

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

2021

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“…6,7) Consequently, the development of additives used in direct powder compression and investigation of tablet-ing conditions have increased. [8][9][10][11][12][13][14] Granulated lactose (GL), intended for use in direct powder compression, has significantly different properties depending on the granulation method and is thought to contribute to handling powder formulations and tablet quality. The correct selection of GL is important to satisfy robustness at a high level when manufacturing solid formulations using a high-speed tableting machine.…”

Section: Introductionmentioning

confidence: 99%

Effects of Granulated Lactose Characteristics and Lubricant Blending Conditions on Tablet Physical Properties in Direct Powder Compression

Nakamura,

Ito,

Sakurada

et al. 2023

CHEMICAL & PHARMACEUTICAL BULLETIN

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Lactose is an excipient used extensively for bulking, diluting, and molding active pharmaceutical ingredients in tablet manufacturing. Particularly, granulated lactose (GL) intended for direct powder compression has distinct properties due to differences in manufacturing methods. It contributes to handling blended powders for tableting and tablet quality. In this study, we aimed to compare the functions of different forms of GL added as excipients during direct powder compression on the tablet properties and the effect of magnesium stearate (Mg-S) used as a lubricant on each type of GL. Different GL types obtained using different manufacturing methods (agitated granulation, GL-AG; spray-dried granulation, GL-SD; fluidized bed granulation, GL-FB) were blended with maize starch, low-substituted hydroxypropyl cellulose, and paracetamol in a V-type blender for 10 min. Mg-S was added at varying amounts (0.1, 1.0, and 2.0%) and blending times (5, 10, and 30 min) for the nine types of blended powders for tableting formulation. The powders were tableted, and the tablets were evaluated for weight and drug loading variations, tensile strength, friability, and disintegration time. When tablets with the same blending conditions were compared, the tensile strength and disintegration time were in the order of GL-FB > GL-SD > GL-AG. For each GL, we analyzed the effects of changes in the added amount of Mg-S and blending time using contour plots, evaluated the effects of blending conditions on tablet properties, and determined the target tablet properties. We investigated the optimization of the lubricant blending conditions to obtain suitable tablets.

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“…To address these problems, in addition to examining formulation and manufacturing conditions, extensive research has focused on improving equipment and developing new additives. [10][11][12][13][14][15][16][17] In recent years, cellulose nanofibers (CNFs), which are made by refining cellulose, the main component of plant cell walls, have attracted attention in various fields as a highperformance biomass material. 18) In Japan, the Ministry of the Environment is promoting a CNF performance evaluation model project aimed at reducing CO 2 emissions, and naturally-derived CNFs extracted from plants are expected to contribute to the realization of a low-carbon society.…”

Section: Introductionmentioning

confidence: 99%

Effect of Powdered Cellulose Nanofiber with Different Particle Sizes on the Physical Properties of Tablets Manufactured <i>via</i> Direct Compression

Nakamura,

Jinno,

Hamaoka

et al. 2023

CHEMICAL & PHARMACEUTICAL BULLETIN

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Direct compression is a tableting technique that involves a few steps in non-demanding manufacturing conditions. High strength and rapid disintegration of tablet formulations were previously achieved through the addition of cellulose nanofibers (CNFs), which have recently attracted attention as a high-performance biomass material. However, CNF addition results in greater variation in tablet weight and drug content, potentially due to differences in particle size between CNF and other additives. Herein, we used pulverized CNF to evaluate the effect of CNF particle size on the variation in tablet weight and drug content. Tablet formulations consisted of CNF with different particle sizes (approximately 100 µm [CNF 100 ] and 300 µm [CNF 300 ], at 0, 10, 30, or 50%), lactose hydrate, acetaminophen, and magnesium stearate. Ten powder formulations with different particle sizes and CNF concentrations were prepared; thereafter, the tablets were produced using a rotary tableting press with a compression force of 10 kN. The variation in weight and drug content as well as the tensile strength, friability, disintegration time, and drug dissolution of tablets were evaluated. CNF 100 addition to the tablets reduced the weight and drug content variation to a greater extent than CNF 300 addition. Using CNF 300 , we produced tablets of sufficient strength and short disintegration time. These properties were also achieved with CNF 100 addition. Our findings suggest that adding CNF of small particle size to the tablet formulation can reduce the variation in weight and drug content while maintaining high strength and short disintegration time.

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Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance

Cited by 9 publications

References 21 publications

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

Effects of Granulated Lactose Characteristics and Lubricant Blending Conditions on Tablet Physical Properties in Direct Powder Compression

Effect of Powdered Cellulose Nanofiber with Different Particle Sizes on the Physical Properties of Tablets Manufactured <i>via</i> Direct Compression

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