Rationale and strategies for formulation development of oral fixed dose combination drug products

Moon, Cheol; Oh, Euichaul

doi:10.1007/s40005-016-0286-4

Cited by 23 publications

(12 citation statements)

References 81 publications

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“…Active film coating is a process to coat a solid dosage unit (tablet or pellet) using a solution or suspension containing APIs as a coating solution. This coating technology meets formulation needs such as rapid drug release or improved product stability and is particularly useful for developing fixed-dose combination (FDC) products to control the drug release rate or physically block interaction between APIs [ 87 , 88 ]. Water-soluble drugs can dissolve in aqueous coating solution or suspension that can then be sprayed on core tablets.…”

Section: Pharmaceutical Application Of Film Coatingmentioning

confidence: 99%

“…Major challenges in active coating include (1) determining the coating end point to achieve target potency, (2) ensuring tablet-to-tablet API content uniformity, and (3) maximizing coating efficiency (ratio of amount of APIs deposited on core tablets to amount of APIs sprayed) [ 13 , 32 , 87 ]. During active film coating, tablets are periodically sampled and analyzed for weight gain as well as the amount of API deposited on core tablets using an in-process assay [ 88 ]. Based on this in-process assay, additional amounts of coating suspension are further sprayed until the coating end-point is reached to obtain the target potency.…”

Section: Pharmaceutical Application Of Film Coatingmentioning

confidence: 99%

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Pharmaceutical Application of Tablet Film Coating

et al. 2020

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Tablet film coating is a common but critical process providing various functionalities to tablets, thereby meeting diverse clinical needs and increasing the value of oral solid dosage forms. Tablet film coating is a technology-driven process and the evolution of coated dosage forms relies on advancements in coating technology, equipment, analytical techniques, and coating materials. Although multiple coating techniques are developed for solvent-based or solvent-free coating processes, each method has advantages and disadvantages that may require continuous technical refinement. In the film coating process, intra- and inter-batch coating uniformity of tablets is critical to ensure the quality of the final product, especially for active film coating containing active pharmaceutical ingredients in the coating layer. In addition to experimental evaluation, computational modeling is also actively pursued to predict the influence of operation parameters on the quality of the final product and optimize process variables of tablet film coating. The concerted efforts of experiments and computational modeling can save time and cost in optimizing the tablet coating process. This review provides a brief overview of tablet film coating technology and modeling approaches with a focus on recent advancements in pharmaceutical applications.

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Section: Pharmaceutical Application Of Film Coatingmentioning

confidence: 99%

Section: Pharmaceutical Application Of Film Coatingmentioning

confidence: 99%

Pharmaceutical Application of Tablet Film Coating

et al. 2020

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“…For diseases that require treatment with multiple drugs, such as CD and UC, fixed-dose combination (FDC) therapy, in which two or more active pharmaceutical ingredients (APIs) are formulated in a fixed proportional manner into a single dosage form, may offer help in addressing some of the problems of compliance. Strategies for development of FDCs are complex and primarily based on fundamental understanding of therapeutic effect of drug combinations, clinical experience, drug-drug interactions, drug-excipient interactions, pharmacokinetic profiles and formulation challenges [9,10]. Although the number of the marketed FDC products has grown over the years and the trend is likely to continue, development of these products is quite demanding.…”

Section: Introductionmentioning

confidence: 99%

“…The reason for such high complexity lies in the fact that the majority of FDC products contain two or more APIs with different physico-chemical and biopharmaceutical properties. To cope with this issue, the rational strategy for development of a new FDC product includes evaluation of pharmacokinetic profiles of APIs as well as development of a simultaneous analytical method for determination of APIs in early phases of FDC development [9,11].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

et al. 2019

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With the increase in the number of medicines patients have to take, there has been a rapid rise of fixed-dose combinations (FDCs) in the last two decades. Prior to FDC development, pharmacokinetic properties of active pharmaceutical ingredients (APIs) have to be evaluated, as well as methods for their determination developed. So as to increase patient compliance in inflammatory bowel disease, three novel FDCs of thiopurine immunosuppressants and folic acid are proposed; physico-chemical and pharmacokinetic properties such as hydrophobicity, lipophilicity and plasma protein binding of all APIs are evaluated. Moreover, experimental results of different properties are compared to those computed by various on-line prediction platforms so as to evaluate the viability of the in silico approach. A simultaneous method for their determination is developed, optimized, validated and applied to commercial tablet formulations. The method has shown to be fast, selective, accurate and precise, showing potential for reliable determination of API content in proposed FDCs during its development.

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“…Fixed dose‐combination (FDC) products, a subset of combination therapies, contain a fixed ratio of 2 or more active ingredients with distinct modes of action formulated into a single dosage form. FDC products contribute to treatment regimens with unique advantages compared to conventional single agent therapies by providing an enhanced clinical efficacy or safety profile, improved patient compliance and convenience, or opportunities for development of novel treatment entities through synergistic action of the components . The understanding of many diseases as containing numerous pathways responsible for the disease has been essential in driving the development of combination therapies, which are capable of targeting these complex networks at multiple sites simultaneously .…”

Section: Introductionmentioning

confidence: 99%

Body of evidence and approaches applied in the clinical development programme of fixed‐dose combinations in the European Union from 2010 to 2016

Nøhr-Nielsen

Bruin

Thomsen³

et al. 2019

Brit J Clinical Pharma

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Aims: To provide insights into the clinical development pathway for fixed-dose combinations (FDCs), to consider strategies, and to elucidate the path to approval by assessing the body of evidence, as summarized in the European Public Assessment Reports. Methods: The main resource was the European Public Assessment Reports for 36 FDCs, which included 239 clinical trials with 157 514 patients. The analyses focused on how prior knowledge of the active substances or combination, use of pharmacokinetic-pharmacodynamic modelling, and clinical trial design choice impact the size and strategy of the clinical development programme.Results: FDC products primarily comprised 2 previously approved components (21/36, 71%) and had only 1 approved combination (21/36, 71%). Utilizing previously approved active substances resulted in fewer clinical trials, arms and patients, but FDC doses studied in the clinical development programme. Furthermore, dosefinding trials were performed for less than half of FDCs consisting of 2 previously approved active substances. The standard approach to demonstrate contribution of active substances was through a factorial or single combination study. Finally, the use of pharmacokinetic modelling showed a significant decrease in the number of FDC doses studied.Conclusions: The field of FDCs seems to be on the rise, utilizing new molecular entities, prior knowledge and re-profiling drugs. However, a way to move FDC development forward might be through new regulatory and scientific paradigms, in which it is encouraged to utilize model-based approaches to develop FDCs with multiple dose levels and dose ratios for exposure-based treatment that will enable personalization.

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Rationale and strategies for formulation development of oral fixed dose combination drug products

Cited by 23 publications

References 81 publications

Pharmaceutical Application of Tablet Film Coating

Pharmaceutical Application of Tablet Film Coating

Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

Body of evidence and approaches applied in the clinical development programme of fixed‐dose combinations in the European Union from 2010 to 2016

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