Pharmaceutical application and development of fixed-dose combination: dosage form review

Kim, Dong-Wook; Weon, Kwon Yeon

doi:10.1007/s40005-021-00543-x

Cited by 23 publications

(24 citation statements)

References 120 publications

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“…In addition, while daily drug injections are inconvenient and result in variable drug biodistributions, we demonstrated that the performance of our designed hybrid spheroids was local and not dependent on the systemic presence of RAP. By that, the administered doses of drugs can be optimized and fixed, regardless the recipient body weight ( 43 ). Given the adverse effects of immunosuppressive drugs, our approach on the localization of hybrid spheroids offers an efficient means of inducing immunotolerance in clinical transplantation field.…”

Section: Discussionmentioning

confidence: 99%

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation

et al. 2022

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Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic- co -glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incubating cell-particle mixture in methylcellulose solution while maintaining high cell viability. RAP-MPs were uniformly distributed in hybrid spheroids and sustainably released RAP for ~3 weeks. Locoregional transplantation of hybrid spheroids containing low doses of RAP-MPs (200- to 4000-ng RAP per recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced programmed death-ligand 1 expression by MSCs was found to be responsible for the immunomodulatory performance of hybrid spheroids. Our results suggest that these hybrid spheroids offer a promising platform for the efficient use of MSCs in the transplantation field.

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Section: Discussionmentioning

confidence: 99%

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation

et al. 2022

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“…Fixed-dose combination (FDC) formulations containing a minimum of two different active ingredients within a dosage form are particularly attractive adherence enhancers to polymedicated patients. The preparation of FDC formulations from a combination of pellets containing different active ingredients can be easily carried out [174,175]; the pellets can also be prepared by a layering process using inert pellet cores [176]. Innovative patient-centric dosage forms, such as medicated straws with layered pellets [177] can also be easily implemented.…”

Section: Future Perspectivesmentioning

confidence: 99%

Review on Starter Pellets: Inert and Functional Cores

et al. 2022

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A significant proportion of pharmaceuticals are now considered multiparticulate systems. Modified-release drug delivery formulations can be designed with engineering precision, and patient-centric dosing can be accomplished relatively easily using multi-unit systems. In many cases, Multiple-Unit Pellet Systems (MUPS) are formulated on the basis of a neutral excipient core which may carry the layered drug surrounded also by functional coating. In the present summary, commonly used starter pellets are presented. The manuscript describes the main properties of the various nuclei related to their micro- and macrostructure. In the case of layered pellets formed based on different inert pellet cores, the drug release mechanism can be expected in detail. Finally, the authors would like to prove the industrial significance of inert cores by presenting some of the commercially available formulations.

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“…Many fixed-dose combination (FDC) products contain two active pharmaceutical ingredients (APIs) in a single dosage form. FDCs improve patient compliance by reducing the “pill burden” . Poor aqueous solubility of the APIs may undermine the oral bioavailability of an FDC.…”

Section: Introductionmentioning

confidence: 99%

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Duggirala

Kumar

et al. 2022

Mol. Pharmaceutics

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Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as model drugs, we designed amorphous solid dispersions (ASDs) for the simultaneous solubility enhancement of two active pharmaceutical ingredients (APIs) by exploiting the drug–drug and drug–polymer interactions. In order to make this approach broadly applicable and over a wide dose range, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 (w/w) were formulated into ternary ASDs. Depending on the dose ratio of the two drugs, the polymer used was either an aminoalkyl methacrylate copolymer (Eudragit, EDE) or polyacrylic acid. The drug–drug and drug–polymer interactions were characterized to be ionic by infrared and solid-state nuclear magnetic resonance spectroscopy. The interactions resulted in a substantial reduction in molecular mobility, evident from the increase in the structural relaxation time determined by dielectric spectroscopy. The drug–drug interaction resulted in ∼3 orders of magnitude reduction in molecular mobility. The addition of a polymer led to a further decrease in molecular mobility of up to 4 orders of magnitude. The strength of intermolecular interactions was also estimated from the glass transition temperatures of the ASDs obtained by differential scanning calorimetry. The strong intermolecular interactions yielded highly stable ASDs with no evidence of crystallization, both at elevated temperatures and under accelerated storage conditions (40 °C/75% relative humidity; 6 weeks). The dissolution performances of the ASDs were evaluated using the area under the curve (AUC) obtained from the concentration–time profiles under the non-sink condition. SMZ and TMP in their ternary ASDs, when compared with their crystalline counterparts, exhibited up to 6.4- and 4.6-fold increases in AUC, respectively. Importantly, the synchronized release of the two drugs was observed, a desirable attribute in synergistic formulations. A single-phase ternary ASD, stabilized by drug–drug and drug–polymer interactions, is likely responsible for the unique release profile.

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Pharmaceutical application and development of fixed-dose combination: dosage form review

Cited by 23 publications

References 120 publications

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation

Review on Starter Pellets: Inert and Functional Cores

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

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