The suitability of disintegrating force kinetics for studying the effect of manufacturing parameters on spironolactone tablet properties

Massimo, Gina; Colombo, Gaia; Nicoli, Sara; Zani, Franca; Colombo, Paolo; Bettini, Ruggero

doi:10.1208/pt040217

Cited by 8 publications

(5 citation statements)

References 5 publications

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“…At higher compression forces, there is a greater volume reduction during tableting resulting in denser tablet matrixes that hold the tablet together more tightly, and reduce water uptake properties, which results in longer disintegration times. Similar results have been observed by Massimo et al (25).…”

Section: Tablet Disintegration and Dissolutionsupporting

confidence: 92%

Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett–Burman Design of Experiments in the Identification of “Main Factors” in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets

et al. 2012

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As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system. Granules were manufactured using an Alexanderwerk WP120 roller compactor and tablets were compressed on a Stokes B2 tablet press. In the early stages of development, prior knowledge was systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA). The factors identified using FMEA were then followed by a quantitative assessed using a Plackett-Burman screening design. Results show that by using prior experience, literature data, and preformulation data the number of experiments could be reduced to an acceptable level, and the use of FMEA and screening designs such as the Plackett Burman can rationally guide the process of reducing the number experiments to a manageable level.

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Section: Tablet Disintegration and Dissolutionsupporting

confidence: 92%

Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett–Burman Design of Experiments in the Identification of “Main Factors” in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets

et al. 2012

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“…In previous studies of octreotide release from PLGA polymers of various molecular weights and lactide:glycolide ratios, pH and impurity content also influenced the percentage of octreotide release [10,11]. Although the very low molecular weight in formulations A and C may be in part offset by a higher amount of lactide monomer, the differences in molecular weights and lactide:glycolide ratios between the three formulations are likely to cause different octreotide release patterns.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide

et al. 2011

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BackgroundSandostatin® LAR® (Novartis Pharma AG) is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid) technology have been developed. This study compares the composition and pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries).FindingsSandostatin LAR exhibited a characteristic concentration-time profile with a limited initial release of octreotide ('burst'), an erosion phase from weeks 3-5, and a slowly declining concentration to day 52. The PK profiles of formulations A and B were characterized by a large initial burst during days 0-2, with up to 41% of the overall area under the plasma-concentration time curve achieved. Low and variable octreotide concentrations were observed during the microparticle erosion phase (days 2-62 [day 82 formulation C]) for formulations A, B and C. Sandostatin LAR microparticles are spherical in shape with an average diameter of approximately 50 μm, determined by scanning electron microscopy evaluation. Formulation A had smaller, irregular microparticles, and formulations B and C exhibited a large range of particle diameters (< 20 to > 100 μm). Inductively coupled plasma-optical emission spectroscopy detected a high tin content of 104 mg/kg in formulation B, the presence of which may suggest inadequate purification following polymer synthesis using tin(II)-octoate as catalyst. PK profiles for formulations A, B and C after a single intramuscular injection of 4 mg/kg in male New Zealand rabbits differed markedly from the PK profile of Sandostatin LAR.ConclusionsClear differences were seen between Sandostatin LAR and formulations A, B and C, including variations in microparticle size, shape and impurity content. Considering the significant differences in the octreotide release profile between Sandostatin LAR and the other formulations, the safety and efficacy of the other formulations cannot be inferred from the Sandostatin LAR efficacy and safety profile; each of these other formulations should be assessed accordingly.

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“…There are also specialized software tools, such as DDDPlus TM software, which considers more specific formulation parameters, including types and amounts of excipients and manufacturing properties (e.g., compression force, tablet diameter) to simulate tablet disintegration and drug particle release rate [18]. In particular, DDDPlus TM software considers that the main mechanism of tablet disintegration is the swelling of the disintegrant particles caused by water uptake into the tablet, which generates a force inside the tablet that eventually leads to the breakage of the bonds between the particles [19]. In order for a drug substance to be absorbed, it must first be released from a dosage form and dissolved in the body fluids, then, diffuse to the site of absorption and, finally, pass through the biological membrane and enter the enterocytes.…”

Section: Interpretation Of Oral Drug Dissolution Permeation and Absor...mentioning

confidence: 99%

Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration

Djuris,

Cvijic,

Djekic

2024

Pharmaceuticals

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The pharmaceutical industry has faced significant changes in recent years, primarily influenced by regulatory standards, market competition, and the need to accelerate drug development. Model-informed drug development (MIDD) leverages quantitative computational models to facilitate decision-making processes. This approach sheds light on the complex interplay between the influence of a drug’s performance and the resulting clinical outcomes. This comprehensive review aims to explain the mechanisms that control the dissolution and/or release of drugs and their subsequent permeation through biological membranes. Furthermore, the importance of simulating these processes through a variety of in silico models is emphasized. Advanced compartmental absorption models provide an analytical framework to understand the kinetics of transit, dissolution, and absorption associated with orally administered drugs. In contrast, for topical and transdermal drug delivery systems, the prediction of drug permeation is predominantly based on quantitative structure–permeation relationships and molecular dynamics simulations. This review describes a variety of modeling strategies, ranging from mechanistic to empirical equations, and highlights the growing importance of state-of-the-art tools such as artificial intelligence, as well as advanced imaging and spectroscopic techniques.

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The suitability of disintegrating force kinetics for studying the effect of manufacturing parameters on spironolactone tablet properties

Cited by 8 publications

References 5 publications

Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett–Burman Design of Experiments in the Identification of “Main Factors” in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets

Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett–Burman Design of Experiments in the Identification of “Main Factors” in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide

Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration

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