1,721,019 research outputs found
Modeling and comparison of release profiles: Effect of the dissolution method
No full textDuring 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
An engineering approach to biomedical sciences: advanced testing methods and pharmacokinetic modeling
Full text linkIn this paper, the philosophy of a research in pharmacology field, driven by an engineering approach, was described along with some case histories and examples. The improvement in the testing methods for pharmaceutical systems (in-vitro techniques), as well as the proposal and the testing of mathematical models to describe the pharmacokinetics (in-silico techniques) are reported with the aim of pointing out methodologies and tools able to reduce the need of expensive and ethical problematic in-vivo measurements
Designing in-vitro systems to simulate the in-vivo permeability of drugs
Full text linkIn this work an engineering approach, consisting in an experimental procedure and a model to derive the data, was presented and applied to improve the testing methods of pharmaceuticals. The permeability of several active molecules have been evaluated across a synthetic membrane. The permeability of these drugs measured through the artificial membrane were successfully correlated to their in-vivo permeability. The relationship with in-vivo permeability was derived, and then a rule to design systems to simulate the intestinal absorption was proposed to reduce the need for expensive and ethical problematic in-vivo measurements
Optimization of chelating agents production process for agricultural administration of inorganic micronutrients
No full textPharmacokinetics of Remifentanil: a three-compartmental modeling approach
Full text linkRemifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes
Controlled drug release from hydrogel-based matrices: Experiments and modeling
Full text linkControlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels.
Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and
diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a
mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work,
the behavior of hydrogel-based matrices has been investigated by means of several experimental
techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed
features were mathematically described using a physical model, defined and recently improved by our
research group (based on balance equations, rate equations and swelling predictions). The agreement
between the huge set of experimental data and the detailed calculations by the model is good, confirming
the validity of both the experimental and the theoretical approaches
In vitro and in silico simulation of human GI behavior in pharmacokinetic studies
No full textIn this work a device which reproduces the mixing in the
stomach due to the peristaltic waves has been realized and
tested using a commercial diclofenac tablet. The tablet has
been found to behave differently depending on the agitation
conditions in comparison with the conventional method.
Moreover, a conventional USP-approved dissolution
apparatus 2 has been equipped with an hollow fibers filter,
in order to allow the simulation of the absorption through
the intestinal wall. The concentration of drug in the donor
compartment has been found lower than that obtained in the
conventional test.
Finally, a PBPK in silico model has been tested and
compared with the experimental data
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