Mohamed AbouGhaly

Abstract Understanding the phase behavior of crystal forms is essential in drug formulation development, as physical stability of the active pharmaceutical ingredient (API) is critical to achieving the desired bioavailability. Solvents greatly impact the physical stability of crystalline solids, resulting in a variety of well-known phase transitions, such as hydrate/solvate formation. However, solvent incorporation may also result in the formation of a less-known crystalline solid solutions (CSSs). The identification and characterization of \{CSSs\} and their effect on \{API\} physicochemical properties have not been investigated. This is the first reported instance of a \{CSS\} for an API. An exhaustive study of the phase behavior of the enantiotropically related polymorphs, I and II, of Benzocaine in water and ethanol revealed that Form I formed a \{CSS\} with water below 294.5 K. Construction of the phase diagrams of Forms I and İI\} in water and ethanol revealed that \{CSS\} formation significantly decreased the phase transition temperature between Forms I and İI\} in water. This change resulted from the increased disorder in the lattice of Form I due to the presence of water. This work demonstrates the importance of understanding the formation of \{CSSs\} on the thermodynamic behavior of crystalline pharmaceutical solids.

Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers—HPMC K4M, Carbopol®, chitosan, or Polyox®—were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p < 0.05) the lowest simulated wetting and in vitro disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p < 0.05) increase in the residence time from 48.44 to 183.76 s. The relative bioavailability was found to be equal to 132.34% relative to the oral tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

ABSTRACTObjectives: This study aims to illustrate the applicability of combined mixture-process variable (MPV) design and modeling for optimization of nanovesicular systems.Methods: The D-optimal experimental plan studied the influence of three mixture components (MCs) and two process variables (PVs) on lercanidipine transfersomes. The MCs were phosphatidylcholine (A), sodium glycocholate (B) and lercanidipine hydrochloride (C), while the PVs were glycerol amount in the hydration mixture (D) and sonication time (E). The studied responses were Y1: particle size, Y2: zeta potential and Y3: entrapment efficiency percent (EE%). Polynomial equations were used to study the influence of MCs and PVs on each response. Response surface methodology and multiple response optimization were applied to optimize the formulation with the goals of minimizing Y1 and maximizing Y2 and Y3.Results: The obtained polynomial models had prediction R2 values of 0.645, 0.947 and 0.795 for Y1, Y2 and Y3, respectively. Contour, Piepel?s response trace, perturbation, and interaction plots were drawn for responses representation. The optimized formulation, A: 265 mg, B: 10 mg, C: 40 mg, D: zero g and E: 120 s, had desirability of 0.9526. The actual response values for the optimized formulation were within the two-sided 95% prediction intervals and were close to the predicted values with maximum percent deviation of 6.2%.Conclusions: This indicates the validity of combined MPV design and modeling for optimization of transfersomal formulations as an example of nanovesicular systems.ABSTRACTObjectives: This study aims to illustrate the applicability of combined mixture-process variable (MPV) design and modeling for optimization of nanovesicular systems.Methods: The D-optimal experimental plan studied the influence of three mixture components (MCs) and two process variables (PVs) on lercanidipine transfersomes. The MCs were phosphatidylcholine (A), sodium glycocholate (B) and lercanidipine hydrochloride (C), while the PVs were glycerol amount in the hydration mixture (D) and sonication time (E). The studied responses were Y1: particle size, Y2: zeta potential and Y3: entrapment efficiency percent (EE%). Polynomial equations were used to study the influence of MCs and PVs on each response. Response surface methodology and multiple response optimization were applied to optimize the formulation with the goals of minimizing Y1 and maximizing Y2 and Y3.Results: The obtained polynomial models had prediction R2 values of 0.645, 0.947 and 0.795 for Y1, Y2 and Y3, respectively. Contour, Piepel?s response trace, perturbation, and interaction plots were drawn for responses representation. The optimized formulation, A: 265 mg, B: 10 mg, C: 40 mg, D: zero g and E: 120 s, had desirability of 0.9526. The actual response values for the optimized formulation were within the two-sided 95% prediction intervals and were close to the predicted values with maximum percent deviation of 6.2%.Conclusions: This indicates the validity of combined MPV design and modeling for optimization of transfersomal formulations as an example of nanovesicular systems.