Papers by Mahmoud Al Omari
Journal of Molecular Structure: THEOCHEM, 2008
Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detai... more Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detailed information on inclusion complex formation between natural cyclodextrins (CDs) and organic molecules (1-alkanols, substituted phenols, and substituted imidazoles). The obtained MD trajectories were used to estimate the binding free energy of each guest/CD complex using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method. The calculated relative binding free energies of the inclusion complexes of some organic compounds with a-and b-CDs were in good agreement with the experimental data though the absolute values were not. Inspection of the binding free energy components revealed the dominant contribution of van der Waals interactions to inclusion complex stability. Both guest-host electrostatic interactions and the hydrophobic effect do also contribute to complex stability. It was also apparent from the calculations that the flexibility of the guest molecule has a significant contribution to complex stability.
Profiles of Drug Substances, Excipients and Related Methodology, 2015
A comprehensive profile of prasugrel HCl is reported herein with 158 references. A full descripti... more A comprehensive profile of prasugrel HCl is reported herein with 158 references. A full description including nomenclature, formulae, elemental analysis, and appearance is included. Methods of preparation for prasugrel HCl, its intermediates, and derivatives are fully discussed. In addition, the physical properties, analytical methods, stability, uses and applications, and pharmacology of prasugrel HCl are also discussed.
Marine Drugs, 2015
This study describes the preparation, characterization and performance of a novel excipient for u... more This study describes the preparation, characterization and performance of a novel excipient for use in oro-dispersible tablets (ODT). The excipient (Cop-CM) consists of chitin and mannitol. The excipient with optimal physicochemical properties was obtained at a chitin: mannitol ratio of 2:8 (w/w) and produced by roll compaction (RC). Differential scanning calorimetry (DSC), Fourier transform-Infrared (FT-IR), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) techniques were used to characterize Cop-CM, in addition to characterization of its powder and ODT dosage form. The effect of particle size distribution of Cop-CM was investigated and found to have no significant influence on the overall tablet physical properties. The compressibility parameter (a) for Cop-CM was calculated from a Kawakita plot and found to be higher (0.661) than that of mannitol (0.576) due to the presence of the highly compressible chitin (0.818). Montelukast sodium and domperidone ODTs produced, using Cop-CM, displayed excellent physicochemical properties. The exceptional binding, fast wetting and superdisintegration properties of Cop-CM, in comparison with commercially available co-processed ODT excipients, results in a unique multifunctional base which can successfully be used in the formulation of oro-dispersible and fast immediate release tablets.
Profiles of Drug Substances, Excipients and Related Methodology, 2011
Profiles of Drug Substances, Excipients and Related Methodology, 2014
Profiles of Drug Substances, Excipients and Related Methodology, 2011
Analytical Profiles of Drug Substances and Excipients, 2001
SILDENAFIL CITRATE Adnan A. Badwan, Lina Nabulsi, Mahmoud M. Al-Omari, Nidal Daraghmeh, and Mahmo... more SILDENAFIL CITRATE Adnan A. Badwan, Lina Nabulsi, Mahmoud M. Al-Omari, Nidal Daraghmeh, and Mahmoud Ashour The Jordanian Pharmaceutical Manufacturing Co. Naor PO Box 94 Amman, Jordan ANALYTICAL PROFILES OF DRUG SUBSTANCES AND ...
Analytical Profiles of Drug Substances and Excipients, 2002
Journal of Solution Chemistry, 2008
The interaction of two benzocycloheptanes namely, pizotifen (Pizo) and ketotifen (Keto), with cyc... more The interaction of two benzocycloheptanes namely, pizotifen (Pizo) and ketotifen (Keto), with cyclodextrins (CDs: α-, β-, γ -, and HP-β-CDs) has been investigated by several techniques including phase solubility, X-ray powder diffractometry, 1 H-nuclear magnetic resonance and molecular mechanical modeling. The effects of CD type, pH, ionic strength and temperature on complex stability were also explored. The complex formation constant (K 11 ) values for the Pizo/CD system follows the decreasing order β-CD > γ -CD > HP-β-CD > α-CD. However, for the Keto/CD system it follows the decreasing order γ -CD > β-CD > HP-β-CD > α-CD. The tendency of Pizo and Keto to complex with β-CD is driven to the extent of 70% by the hydrophobic effect. Complex formation of Keto and Pizo was substantially driven by entropy (>100 J·mol −1 ·K −1 ) but slightly retarded by enthalpy (3-8 kJ·mol −1 ). 1 H-NMR and MM + studies indicate multimodal inclusion of the methylpiperadine, thiophene and phenyl moieties into the β-CD cavity.
Journal of Solution Chemistry, 2009
... Analysis Ameer Ghuzlaan · Mahmoud M. Al Omari · Khaldoun A. Al-Sou'od Received .... more ... Analysis Ameer Ghuzlaan · Mahmoud M. Al Omari · Khaldoun A. Al-Sou'od Received ... mass. Initially, the position of the CD macrocycle was fixed whereas the guest approached along the x-axis toward the wider rim of the CD cavity. The ...
Journal of Solution Chemistry, 2009
Guest-host interactions of haloperidol (Halo) with β-cyclodextrin (β-CD) have been investigated u... more Guest-host interactions of haloperidol (Halo) with β-cyclodextrin (β-CD) have been investigated using several techniques including phase solubility diagrams (PSD), proton nuclear magnetic resonance ( 1 H-NMR), X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and molecular mechanical modeling (MM + ).
Journal of Solution Chemistry, 2008
Guest-host interaction of astemizole (Astm) with cyclodextrins (CDs) has been investigated using ... more Guest-host interaction of astemizole (Astm) with cyclodextrins (CDs) has been investigated using phase solubility diagrams (PSD), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), proton nuclear magnetic resonance ( 1 H-NMR) and molecular mechanical modeling (MM + ). Estimates of the complex formation constant, K 11 , show that the tendency of Astm to complex with CDs follows the order: β-CD > HP-β-CD > γ -CD, α-CD. 1:1 Astm/β-CD complex formation at pH = 5.0 was largely driven by the hydrophobic effect (desolvation), which was quantitatively estimated at −16.5 kJ·mol −1 , whereas specific interactions contribute only −5.3 kJ·mol −1 to 1:1 complex stability ( G o 11 = −22.7 kJ·mol −1 ). The percentage contributions of the hydrophobic effect and specific interactions were therefore 73 and 27%, respectively. Both enthalpic and entropic factors contribute equally well (−11 kJ·mol −1 each) to 1:1 Astm/β-CD complex stability. 1 H-NMR and MM + molecular modeling studies indicate the formation of different isomeric 1:1 and 1:2 complexes. The dominant driving force for complexation is evidently van der Waals with very little electrostatic contribution. PSD, 1 H-NMR, DSC, XRPD and MM + studies proved the formation of inclusion complexes in solution and the solid state.
Journal of Solution Chemistry, 2007
Guest-host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo... more Guest-host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: a-CD, b-CD, c-CD and 2-hydroxypropyl-bcyclodextrin (HP-b-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20°C, and with b-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid-base ionization constants (pK a s) for Diclo in the presence and absence of b-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with a-, b-, and HP-b-CD. In contrast, Diclo forms soluble 1:1 Diclo/c-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/c-CD, but the 1:1 complex saturates at 5.8 mM c-CD with a solubility product constant (pK sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: c-CD > HP-b-CD > b-CD > a-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with c-CD, where the overall concentration of the latter exceeds 5.8 mM c-CD. Both 1 H-NMR spectroscopic and molecular mechanical modeling (MM + ) studies of Diclo/b-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.
Journal of Pharmaceutical and Biomedical Analysis, 2006
Guest-host interactions of sildenafil (Sild) with cyclodextrins (CyDs) have been investigated usi... more Guest-host interactions of sildenafil (Sild) with cyclodextrins (CyDs) have been investigated using several techniques including phase solubility diagrams (PSD), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), proton nuclear magnetic resonance ( 1 H NMR) and molecular mechanical modeling (MM + ). Estimates of the complex formation constant (K 11 ) show that the tendency of Sild to complex with CyDs follows the order: -CyD > HP--CyD > ␥-CyD, ␣-CyD, where K 11 values at pH 8.7 and 30 • C were 150, 68 and 46, 43 M −1 , respectively. Ionization of Sild reduces its tendency to complex with -CyD, where protonated (at pH 3.6) and anionic Sild (at pH 12.1) species have K 11 values of 17 and 42 M −1 , respectively, compared with 150 M −1 for neutral Sild (at pH 8.7). The hydrophobic character of Sild was found to provide 39% of the driving force for complex stability, while other factors including specific interactions contribute −7.9 kJ/mol. Complex formation of Sild with -CyD ( G • = −22.9 kJ/mol) is largely driven by enthalpy ( H • = −19.8 kJ/mol) and slight entropy ( S • = 10.3 J/mol K) changes. 1 H NMR and MM + studies indicate formation of two isomeric 1:1 complexes: one involving complete inclusion of the phenyl-moiety into the -CyD cavity while the other pertaining to partial inclusion of the pyrimidinone moiety. The dominant driving force for complexation is evidently van der Waals with very little electrostatic contribution. DSC, XRPD and 1 H NMR studies proved the formation of inclusion complex in solution and the solid state.
Journal of Pharmaceutical and Biomedical Analysis, 2002
There is a lack of information concerning analysis of terbutaline sulfate and quantification of i... more There is a lack of information concerning analysis of terbutaline sulfate and quantification of its related substances particularly in the liquid dosage forms. This work aimed at developing and validating an HPLC method for determination of terbutaline sulfate and its possible degradation products, namely, 3,5-dihydroxybenzoic acid, 3,5 dihydroxybenzaldehyde and 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone that might appear as impurities in the starting material as well as in the solid and liquid formulations. The chromatographic system used consisted a Hypersil 100 C 18, 150×4.6 mm (5 mm) column, a mobile phase of ammonium acetate (0.15 M) and glacial acetic acid (pH of 4.0, 96:4 v/v) with a flow rate of 2 ml min − 1 and a UV detector set at 270 nm. The degree of linearity and the characteristic statistical parameters of the calibration curves including the limit of detection (LOD) and limit of quantitation (LOQ) were estimated for terbutaline sulfate and its degradation products. The method was found to be specific, stability indicating, accurate, precise and robust.
Journal of Pharmaceutical and Biomedical Analysis, 2011
Journal of Pharmaceutical and Biomedical Analysis, 2001
The chemical stability of enalapril maleate in tablet dosage forms consisting of different formul... more The chemical stability of enalapril maleate in tablet dosage forms consisting of different formulation excipients has been studied in this work. The influence of various parameters such as heat, moisture, light and the drug-matrix was investigated. The degradation of enalapril maleate has been followed by using an HPLC method, which was demonstrated to be specific, stability indicating, accurate and precise. The degradation kinetics of enalalpril maleate in phosphate buffer solutions of pH values in the range of 2.2-10.5 were observed to be psuedo first order throughout the whole pH range studied. Enalapril maleate alone showed high stability for temperature under dry and humid conditions, however it became unstable when mixed with the drug-matrix in its tablet formulations and exposed to the same conditions. The pathway of degradation of enalapril maleate was found to be pH dependent. The extent of degradation of two different enalapril maleate tablet formulations (product A of a basic drug-matrix and product B of an acidic drug-matrix) has been investigated. The degree of degradation of the product with acidic matrix was significantly less than that of the basic matrix under same temperature and humidity conditions. Infact, diketopiperazine and enalaprilat degradants were mainly associated with the degradation of the product with the acidic matrix and that with the basic matrix, respectively. Dry enalapril maleate powder showed some photolysis, which was more significant with daylight (3.3%) compared with that under UV light (0.2%). Although the product with the acidic matrix showed some photolysis but the effect was not pronounced and the % recovery of enalapril was almost complete and within the acceptable experimental errors. However, the product with the basic matrix showed almost no response for photolysis.
Journal of Pharmaceutical and Biomedical Analysis, 2001
This study aimed at developing and validating an HPLC method for the assay of sildenafil citrate ... more This study aimed at developing and validating an HPLC method for the assay of sildenafil citrate and its related substances that might coexist in the drug commercial products and in tablets' formulation as impurities that originate from synthesis processes or degradation. A chromatographic system comprising a mBondapak C 18 (10 mm) column, a mobile phase of ammonium acetate (pH 7.0, 0.2 M)-acetonitrile (1:1, v/v), a flow rate of 1 ml/min and a UV detector set at 240 nm has shown good chromatographic separation for sildenfil and the other related substances. The degree of linearity of the calibration curves, the percent recoveries of sildenafil and related substances, the limit of detection, LOD, and limit of quantitation, LOQ for the HPLC method have been determined. The HPLC method under study was found to be specific, precise, accurate, reproducible indicating stability and robust.
Journal of Pharmaceutical and Biomedical Analysis, 2007
The chemical stability of montelukast (Monte) in solution and in its solid state was studied. A s... more The chemical stability of montelukast (Monte) in solution and in its solid state was studied. A simultaneous measurement of Monte and its degradation products was determined using a selective HPLC method. The HPLC system comprised a reversed phase column (C18) as the stationary phase and a mixture of ammonium acetate buffer of pH 3.5 and methanol (15:85 v/v) as the mobile phase. The UV detection was conducted at 254 nm.
Journal of Molecular Liquids, 2010
A measurement of the hydrophobic character of the drug substrate, henceforward termed as the hydr... more A measurement of the hydrophobic character of the drug substrate, henceforward termed as the hydrophobic effect (HE), to complex stability is established through the observed linear correlation of the free energy of 1:1 complex formation (ΔG K 11 = −RTlnK 11
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Papers by Mahmoud Al Omari