@article{Cascone2017,

title = {Modeling and comparison of release profiles: Effect of the dissolution method},

author = {Sara Cascone},

url = {http://www.sciencedirect.com/science/article/pii/S092809871730355X},

doi = {10.1016/j.ejps.2017.06.021},

issn = {0928-0987},

year  = {2017},

date = {2017-08-30},

journal = {European Journal of Pharmaceutical Sciences},

volume = {106},

pages = {352-361},

abstract = {During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.

Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.},

keywords = {drug release, In silico, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2016,

title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation},

author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659

},

doi = {10.1016/j.jddst.2016.08.002},

issn = {1773-2247},

year  = {2016},

date = {2016-10-01},

journal = {Journal of Drug Delivery Science and Technology},

volume = {35},

pages = {272-283},

abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.



This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.},

keywords = {Biodistribution, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Piazza2016b,

title = {The effect of liver esterases and temperature on remifentanil degradation in vitro},

author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191},

doi = {10.1016/j.ijpharm.2016.06.043},

year  = {2016},

date = {2016-07-04},

journal = {International Journal of Pharmaceutics},

volume = {510},

number = {1},

pages = {359\textendash364},

abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.},

keywords = {In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2012d,

title = {In vitro simulation of drug intestinal absorption.},

author = { Gaetano Lamberti and Sara Cascone and Margherita Iannaccone and Giuseppe Titomanlio},

url = {http://www.sciencedirect.com/science/article/pii/S0378517312009520},

doi = {10.1016/j.ijpharm.2012.10.012},

issn = {1873-3476},

year  = {2012},

date = {2012-12-01},

journal = {International journal of pharmaceutics},

volume = {439},

number = {1-2},

pages = {165--8},

abstract = {In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.},

keywords = {Controlled drug release, In vitro, Intestinal Absorption, Mass balance, Oral administration, Pharmacokinetics, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2011,

title = {The influence of dissolution conditions on the drug ADME phenomena.},

author = { Sara Cascone and Felice De Santis and Gaetano Lamberti and Giuseppe Titomanlio},

url = {http://www.sciencedirect.com/science/article/pii/S093964111100141X},

doi = {10.1016/j.ejpb.2011.04.003},

issn = {1873-3441},

year  = {2011},

date = {2011-10-01},

journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f\"{u}r Pharmazeutische Verfahrenstechnik e.V},

volume = {79},

number = {2},

pages = {382--91},

abstract = {In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.},

keywords = {ADME, Dissolution, Enteric coated, In silico, In vitro, Pharmacokinetic modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}