| 1. |
- Alomari, Mustafa, et al.
(författare)
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Printing of T3 and T4 Oral Drug Combinations as a Novel Strategy for Hypothyroidism
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 549:1-2, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T3) and thyroxine (T4) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) printing is a potential solution to enable the dual deposition of T3 and T4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T3 and T4. Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T3 (15–50 μg) and T4 dosages (60–180 μg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T3 and T4 (R2 = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (< 45 seconds). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T3 and T4 onto the same substrate for oral administration.
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| 2. |
- Elbadawi, Moe, et al.
(författare)
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3D printing tablets : Predicting printability and drug dissolution from rheological data
- 2020
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 590
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Tidskriftsartikel (refereegranskat)abstract
- Rheology is an indispensable tool for formulation development, which when harnessed, can both predict a material’s performance and provide valuable insight regarding the material’s macrostructure. However, rheological characterizations are under-utilized in 3D printing of drug formulations. In this study, viscosity measurements were used to establish a mathematical model for predicting the printability of fused deposition modelling 3D printed tablets (Printlets). The formulations were composed of polycaprolactone (PCL) with different amounts of ciprofloxacin and polyethylene glycol (PEG), and different molecular weights of PEG. With all printing parameters kept constant, both binary and ternary blends were found to extrude at nozzle temperatures of 130, 150 and 170 C. In contrast PCL was unextrudable at 130 and 150 C. Three standard rheological models were applied to the experimental viscosity measurements, which revealed an operating viscosity window of between 100-1000 Pa.s at the apparent shear rate of the nozzle. The drug profile of the printlets were experimentally measured over seven days. As a proof-of-concept, machine learning models were developed to predict the dissolution behaviour from the viscosity measurements. The machine learning models were discovered to accurately predict the dissolution profile, with the highest f2 similarity score value of 90.9 recorded. Therefore, the study demonstrated that using only the viscosity measurements can be employed for the simultaneous high-throughput screening of formulations that are printable and with the desired release profile.
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| 3. |
- Sousa, Tiago, et al.
(författare)
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The gastrointestinal microbiota as a site for the biotransformation of drugs
- 2008
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 363:1-2, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- There are 100 trillion microbes in the human gastrointestinal tract with numbers increasing distally. These microbiota secrete a diverse array of enzymes (primarily for carbohydrate and protein fermentation) giving them substantial metabolic potential which can have major implications for drug stability. At least thirty drugs which are, or have been, available commercially, were subsequently shown to be substrates for these bacterial enzymes, and with increasing numbers of new and existing drugs having the potential for contact with the distal gut (through modified release systems or poor solubility/permeability), many more are expected to be discovered. The major concern with bacterial drug degradation is the behaviour of the metabolite; is it more or less active than the parent compound, or has toxicity resulted? For example, there were eighteen deaths in 1993 due to a drug interaction in which a toxic drug metabolite was produced by bacterial fermentation. Thus, the objective of this review is the provision of a comprehensive overview of this area; the gastrointestinal microbiota, their drug substrates and metabolic mechanisms, and approaches to studying this further are discussed.
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| 4. |
- Vuddanda, Parameswara Rao, et al.
(författare)
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Personalisation of warfarin therapy using thermal ink-jet printing
- 2018
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 117, s. 80-87
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Tidskriftsartikel (refereegranskat)abstract
- Warfarin is a widely used anticoagulant that is critical in reducing patient morbidity and mortality associated with thromboembolic disorders. However, its narrow therapeutic index and large inter-individual variability can lead to complex dosage regimes. Formulating warfarin as an orodispersible film (ODF) using thermal ink-jet (TIJ) printing could enable personalisation of therapy to simplify administration. Commercial TIJ printers are currently unsuitable for printing the milligram dosages, typically required for warfarin therapy. As such, this study aimed to modify a commercial TIJ printing system to formulate personalised warfarin ODFs containing therapeutic dosages. A TIJ printer was modified successfully with the printer functionality intact; the substrate (paper) rolling mechanism of the printer was replaced by printing onto a stationary stage. Free film substrates were composed of hydroxypropyl methylcellulose (20%w/w) and glycerol (3%w/w). The resulting ODFs were characterised for morphology, disintegration, solid-state properties and drug content. Printed film stability was assessed at 40 °C/75% relative humidity for 30 days. Therapeutic warfarin doses (1.25 and 2.5 mg) were successfully printed onto the film substrates. Excellent linearity was observed between the theoretical and measured dose by changing the warfarin feed concentration (R2 = 0.9999) and length of the print objective, i.e. the Y-value, (R2 = 0.9998). Rapid disintegration of the ODFs was achieved. As such, this study successfully formulated personalised warfarin ODFs using a modified TIJ printer, widening the range of applications for TIJ printing to formulate narrow therapeutic index drugs.
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