Mohamed AbouGhaly

Inflammatory bowel disease (IBD) is a debilitating condition characterized by chronic inflammation of the colon which can increase the risk of colon cancer. Celecoxib (CXB), a cyclooxygenase-2 inhibitor, showed potential for the prophylaxis against IBD. However, it suffers from poor aqueous solubility and cardiovascular toxicity on prolonged use. Here, CXB solubility was enhanced using nanomixed micelles (NMMs) and then colon targeted in a pulsatile system to minimize systemic side effects. Pluronic P123 NMMs with bile salts or hydrophilic Pluronics were prepared using the thin film hydration technique. NMMs were characterized for particle size, size distribution and zeta potential before and after freeze drying and for solubility enhancement. The freeze dried NMMs were then loaded in pulsatile systems with varying tablet plugs containing time-dependent polymers at different concentrations. The optimum NMM consisted of Pluronic P123 and sodium taurocholate (1:1) and CXB:surfactant mixture ratio of 1:30. The pulsatile capsules, containing a tablet plug made of 75% Carbopol®, achieved the target release profile with 88.35% of the dose released after an 8 hrs lag period. Finally, the optimum NMM/pulsatile system showed protective effect against experimentally-induced colitis compared to conventional capsules and pulsatile capsules filled with pure CXB.

Deuterium incorporation in solid-state hydrogen deuterium exchange with mass spectrometry (ssHDX-MS) has been correlated with protein aggregation on storage in sugar-based solid matrices. Here, the effects of sucrose, arginine and histidine buffer on the rate of aggregation of a lyophilized monoclonal antibody (mAb) were assessed using design of experiments (DoE) and response surface methodology. Lyophilized formulations were characterized using ssHDX-MS and Fourier transform infrared spectroscopy (ssFTIR) to assess potential correlation with stability in solid state. The samples were subjected to storage stability at 5 °C and stressed stability at 40 °C/75% RH for 6 months, and the aggregation rate was measured using size exclusion chromatography (SEC). Different levels of arginine had no significant effect on deuterium uptake in ssHDX-MS, although stability studies showed that aggregation rate decreased with increasing arginine concentration. Similarly, when histidine buffer was replaced with phosphate buffer at the same pH and molarity, ssHDX-MS showed no differences in deuterium uptake, but storage stability studies showed a significant increase in aggregation rate. The results suggest that proteins can be stabilized in amorphous solids by ionic interactions which ssHDX-MS does not detect, an important indication of the limitations of the method.

AbstractThe ability to engineer biocompatible polymers with controllable properties is highly desirable. One such approach is to cross-link carbohydrate polymers using ionotropic gelation (IG). Previous studies have investigated the effect of curing time on alginate cross-linking. Herein, we discuss a novel study detailing the effect of IG residence time (IGRT) on the cross-linking of alginate with calcium ions (Ca2+) along with water migration (syneresis) and their subsequent impact on the pharmaceutical properties of alginate particles. IGRT was shown to have a significant effect on particle size, porosity, density, mechanical strength and swelling of calcium alginate particles as well as drug release mechanism. Furthermore, we describe a novel application of electron dispersive spectroscopy (EDS), in conjunction with Fourier Transform- infra red (FT-IR) spectroscopy, to analyze and monitor the changes in Ca2+ concentration during cross-linking. A simple procedure to determine the concentration and distribution of the surface and internal Ca2+ involved in alginate cross-linking was successfully developed.

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.

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.

ObjectivesThe purpose of the current study was to clinically and radiographically assess the regenerative potential of metformin in enhancement of bone healing in third molar extraction sites.
Patients and methods
The present study included 40 healthy volunteers (27 females and 13 males) aged 21-27 years who had been scheduled for surgical removal of their impacted mandibular third molars. Volunteers were randomly assigned to either groups A or B. Twenty patients of group A (test) underwent surgical removal of impacted mandibular third molar followed by application of metformin gel in the surgical site. Twenty patients of group B (control) underwent surgical removal of impacted mandibular third molar only. Clinical and radiographic evaluation (cone beam computed tomography) was performed immediately after operation and at 6 months postoperatively in terms of the probing pocket depth, the bone defect length at the distal side of second lower molars, and bone density. Data were collected and statistical analysis was performed.
Results
At 6 months postoperatively group A (test) showed significantly higher (P ≤ 0.001) mean bone density compared with group B (control). On the other hand, there was nonsignificant (P ≥ 0.001) difference in the periodontal pocket depth and defect length between the test and control groups after 6 months.
Conclusion
There was a significant improvement regarding bone density at the surgical site using metformin after impacted mandibular third molar removal. Thus bone-formative effects of the common oral antihyperglycemic agent MF can provide a new direction in the field of bone healing.

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.