Inclusion Complexation and Dissolution Properties of Nimesulide and Meloxicam–hydroxypropyl-β-cyclodextrin Binary Systems

The purpose of the work is physicochemical characterization of nimesulide (NI) and meloxicam (ME)–hydroxypropyl-β-cyclodextrin (HP-β-CD) binary systems both in solution and solid states and to improve the pharmaceutical properties of NI and ME via inclusion complexation with HP-β-CD. Binary systems of NI and ME with HP-β-CD have been characterized both in solution and solid state by different physicochemical methods. Three types of drug–HP-β-CD binary systems, namely physical mixtures (PM), kneaded systems (KS) and co evaporated systems (CS) in 1:1 and 1:2 molar ratios (1:1 and 1:2 M) were prepared. Phase solubility and ¹H-NMR spectroscopic studies in solution state revealed 1:1 M complexation of NI and ME with HP-β-CD. A partial inclusion of NI with HP-β-CD at both molar ratios of kneaded and co evaporated systems and a true inclusion of ME with HP-β-CD at both molar ratios of co evaporated systems in solid state was confirmed by differential scanning calorimetry (DSC), powder X-ray diffractometry (powder X-RD) and scanning electron microscopy (SEM) studies. Dissolution properties of NI and ME–HP-β-CD binary systems were superior when compared to corresponding pure drugs. The aqueous solubility and dissolution properties of NI and ME can be improved by inclusion complexation with HP-β-CD. Author for correspondence: E-mail: nbnaid2@E-mail.uky.edu     

A novel, tandem construction of C-N and C-C bonds: facile and one-pot transformation of the Baylis-Hillman adducts into 2-benzazepines

A novel reaction involving tandem construction of C-N and C-C bonds via the simultaneous Ritter and Houben-Hoesch reactions on Baylis-Hillman adducts leading to a convenient, one-pot synthesis of 2-benzazepine derivatives is described. A facile stereoselective transformation of the Baylis-Hillman adducts into (E)- and (Z)-allyl amides is also presented.     

Platinum group metal functionalized phosphine complexes. Part 2. Phosphinoamide rhodium(I), iridium(I), palladium(II) and platinum(II) complexes

Summary Rhodium(I), iridium(I), palladium(II) and platinum(II) complexes of the phosphinoamide ligands, Ph₂PCH₂CONHR (R = H, HDPA; Me, MDPA; Ph, PDPA) were prepared and characterized by using conductivity data, i.r., ¹H and ³¹P(H) n.m.r. spectral data. Reaction of the ligands with MCl(PPh₃)₃ and MCl(CO)(PPh₃)₂ (M = Rh, Ir) in CH₂Cl₂ under reflux lead to the formation of MCl(PPh₃)₂ [Ph₂PCH₂C(O)NHR] and MCl(CO)(PPh₃)[Ph₂PCH₂–C(O)HNR] respectively. The reaction of either K₂MCl₄ or cis-MCl₂(PPh₃)₂ affords complexes of the type cis-MCl₂[Ph₂PCH₂C(O)NHR]₂ (M = Pd, Pt). A similar product results even from the reaction of phosphinoamides with cis-platin. Possible structures are proposed for the complexes based on their physicochemical data     

Extraction and spectrophotometric determination of vanadium(V) with 8-hydroxyquinoline

The extraction and spectrophotometric determination of vanadium (V) with oxine is investigated at higher acidities than described previously. Under these conditions, n-butanol and other alcohols are found to exert a synergic effect on the extraction of vanadium into benzene. In the presence of alcohol only a 6-fold ligand excess is needed for quantitative extraction in a single operation, the acidity of the aqueous medium being 0.05M with respect to sulphuric or phosphoric acid. The interference of iron(III) in the spectrophotometric determination of vanadium is suppressed by the addition of pyrophosphate. Beer's law is obeyed up to 14.0 mug of vanadium/ml and the sensitivity is 0.008 mug of vanadium/cm(2) at 390 mmu. The composition of the extracted species is found to be vanadium:oxine:n-butanol = 1:2:2.     

Platinum group metal functionalized phosphine complexes. Part 1: Phosphinoamide ruthenium(II) complexes

Summary Three new bifunctional phosphinoamide ligands of the type Ph₂PCH₂C(O)NHR (R = H, HDPA; Me, MDPA; Ph, PDPA) were prepared and characterized. Their ruthenium(II) complexes prepared from two different precursors, RuCl₂-(DMSO)₄ and RuCl₂(PPh₃)₃, are of similar composition and correspond to the formula, [RuCl(L)₂(P-O)₂]Cl (L = DMSO/PPh₃; phosphinoamide). However, RuCl₃-(AsPh₃)₂(MeOH) reacts with the phosphinoamide to yield a reduced product of the cis-RuCl₂(P-O)₂ type. The ligands and complexes were characterized by mass, i.r. and n.m.r. spectroscopy. Possible stereochemistries for the complexes are proposed.     

Biomimetic Model of Coenzyme B12: Aquabis(ethane‐1,2‐diamine‐κN,κN′)ethylcobalt(III) – Its Kinetic and Binding Studies with Imidazoles and Amino Acids and Interactions with CT DNA

Pseudo‐first‐order reaction kinetics and binding studies of trans‐[Co(en)₂(Et)H₂O] complex with 1H‐imidazole, substituted 1H‐imidazoles, histidine, histamine, glycine and glycine ethyl ester were investigated by means of spectrophotometric techniques. Equilibrium constants were determined as a function of pH at 25°. Binding and kinetic studies were correlated to basicity and steric hindrance. From the equilibrium data, it was found that the entering nucleophile is participating in the transition state, an I_d mechanism is proposed. The effect of the incoming ligands on the complex was studied by molecular mechanics. The interaction of trans‐[Co(en)₂(Et)H₂O] with CT DNA was studied spectrophotometrically.     

A Validated Stability Indicating LC Method for Mitotane in Bulk Drugs and Pharmaceutical Dosage Forms

A novel, sensitive, stability indicating RP-LC method has been developed for the quantitative determination of mitotane, its impurity in both bulk drugs and pharmaceutical dosage forms. Efficient chromatographic separation was achieved using a C18 stationary phase with simple mobile phase combination delivered in an isocratic mode and quantitation was by ultraviolet detection at a wavelength of 230 nm. The mobile phase consisted of buffer and acetonitrile (25:75, v/v) delivered at a flow rate of 1.0 mL min⁻¹. Buffer consisted of 10 mM potassium dihydrogen orthophosphate monohydrate, pH adjusted to 2.5 by orthophosphoric acid. In the developed LC method the resolution (R _s ) between mitotane and its impurity namely Imp-1 was found to be greater than 2.5. Regression analysis shows an r value (correlation coefficient) greater than 0.999 for mitotane and its impurity. This method was capable to detect the impurity of mitotane at a level of 0.003% with respect to test a concentration of 0.2 mg mL⁻¹ for a 10 μL injection volume. The inter- and intra-day precision values for mitotane and its impurity was found to be within 2.0% RSD. The method has shown good and consistent recoveries for mitotane in bulk drugs (99.2–101.5%), pharmaceutical dosage forms (98.2–103.1%) and for its impurity (99.7–102.1%). The test solution was found to be stable in diluent for 48 h. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in basic stress hydrolysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.97%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

     

Chemoselective hydrolysis of terminal isopropylidene acetals in acetonitrile using molecular iodine as a mild and efficient catalyst

A simple, mild and efficient method for deprotection of acetonides in the presence of molecular iodine is described. Acid labile protecting groups such as PMB, OMe, OBn, allyl and propargyl are compatible with the reaction conditions, while TBS, TBDPS, TMS and THP ethers were unstable under the same conditions.