Biopharmaceutical classification of desloratadine – not all drugs are classified the easy way

Abstract

<jats:title>Abstract</jats:title><jats:p>The biopharmaceutical classification of drugs was designed as a basis for bio-waivers – a mechanism with the double ethical benefit of delivering new drug formulations to the market with less human testing and lower cost. However, many drugs defy simple classification because <jats:italic>in vitro</jats:italic> permeability and stability assessment can be challenging as shown in this study for desloratadine. Literature shows that desloratadine is highly soluble, while data on luminal stability and permeability are circumstantial. Combined with borderline bioavailability and not really known fraction of absorbed dose, desloratadine was found to be a good example for showing the innovative <jats:italic>in vitro</jats:italic> approaches necessary to unambiguously classify desloratadine according to Biopharmaceutical Classification System (BCS) guideline. Presented study undoubtedly confirmed that desloratadine solubility is high and dissolution is very rapid for immediate release reference tablets. We have demonstrated deslorata-dine stability under legally required conditions and also in more physiologically relevant media. High <jats:italic>in vitro</jats:italic> desloratadine permeability was confirmed using Caco-2 and Parallel Artificial Membrane Permeability Assay (PAMPA). Well-established <jats:italic>in vitro</jats:italic> model with rat intestinal tissue could not be used due to reasons elaborated in this paper.</jats:p>

A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies

“…(n=4) [18] . Although these findings indicate the low permeability compared to Metoprolol tartrate, which is used as a reference for permeability classification [19] , the effect of the formulation on the permeability of MLP should be assessed by comparing the permeability of MLP in solution and formulation with further evaluation [19] , [20] , [21] .…”

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery

“…43,44 Pre-surgery simulations were performed using the default ACAT inputs, except for the percent fluid volumes in the small intestine (23%) and colon (0.5%), which were taken from the literature. 45 The additional ACAT model adjustments for postbariatric patients included stomach pH value (increased from optimized to match the simulated human plasma concentration profile; in accordance with the literature data 64 55 optimized to match the simulated human plasma concentration profile, in accordance with the literature data 62 clearance, CL (L/h/kg) 6 optimized to match the simulated human plasma concentration profile, while keeping the optimized values within the range of the literature-reported data 65,66 0.8 optimized to match the simulated human plasma concentration profile while keeping the optimized values within the range of the literature-reported data 53,67 volume of distribution, V d (L/kg) 4 optimized to match the simulated human plasma concentration profile, while keeping the optimized values within the range of the literature-reported data 65,66 10 optimized to match the simulated human plasma concentration profile while keeping the optimized values within the range of the literature-reported data 53,67 distribution constant, k…”

An exploration on retro-construction of plasma drug concentration-time curves from corresponding urine excretion data and single-point plasma concentrations using a simplified and idealized method

“…Terminal elimination half-life (h) ~8.5 ( 21) 27 (22) Urinary excretion (% of radioactive dose) 41% (22,36) 30% (37) Urinary excretion (% of dose) <2% ( 38) <2% (37) Faecal excretion (% of radioactive dose) 47% (22,36) Faecal excretion (% of dose) <7% (38) Negligible (37) MW, molecular weight, in Dalton; pKa, acid-base dissociation constant; B/P, blood plasma distribution ratio; Fu,p, fraction of unbound in plasma; Vss, volume of distribution at steady state; CL/F, bioavailability-corrected clearance.…”