Drug analysis

Abstract

a n d m e t h o d s i n c h a r a c t e r i z a t i o n a n d d e e p s t u d i e s o n t h e polymorphic state of drug substances. The book is divided into six main sections: the first deals with thermodynamics and theoretical issues including characterization of polymorphic and solvatomorphic systems along with computational methodologies for prediction of the crystal polymorph state of drugs. The second section covers preparative methods for polymorphs and solvatomorphs, where the classical as well as High-Throughput approaches are discussed, with practical examples and the automation potential for scientific and development applications. The structural properties of polymorphs and solvatomorphs, including structural aspects and pharmaceutical co-crystal structures, are discussed in the third section. The characterization of polymorphs and solvatomorphs is a key aspect covered in the fourth section. Modern analytical approaches such as thermoanalytical and crystallographic methods, vibrational spectroscopy, solid-state NMR spectroscopy are included with brief descriptions of the effect of polymorphism and solid-state salvation on important pharmaceutical parameters such as dissolution and solubility of drugs. The fifth section encompasses the interconversion of polymorphs and solvatomorphs as well as the effects of pharmaceutical processing on the solid form of drug and excipient material. The former covers interconversions such as solid-to-solid, dehydration and desolvation, solution and vapor-mediated phase transformation. While the latter embraces processes involved in pharmaceutical manufacture such as milling, granulation, drying, hydration, lyophilization, compression and other shear stress in polymorph and solvatomorph interconversion.

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

“…Askin et al designed a protocol to synthesize new imidazole [2,1b] [1,3,4]thiadiazoles (73)(74)(75)(76)(77)(78)(79)(80)(81). Initially substituted benzyl chloride derivatives (62)(63)(64) were refluxed with KOH in presence of ethanol for 4-6 h to obtain 2-amino-1,3,4-thiadiazoles (66)(67)(68) Newly synthesized compounds were tested for their inhibitory activity against hCA I and hCA II by taking standard AAZ and THA and it was observed that compound 70b and 71 were found to be most potent against hCA I with K i values of 23.44 ± 4.92 and 51.53 ± 10.74 nM, respectively.…”

“…Initially, isatin derivatives 101(a-c) treated with KI and K 2 CO 3 in presence of DMF and were refluxed for 4-6 h to yield N-alkylated isatin derivatives 102(a-o) and were further reacted with thiosemicarbazide, 1,4-dioxane Cs 2 CO 3 along with refluxing to synthesize compounds N-alkylated triazino [5,6-b]indolethioether derivatives 103(a-o). Second, compounds 103(a-o) were reacted with propargyl bromide to produce compounds N-alkyl-3-prop-2-yn-1-ylthio)-5H- [1,2,4]triazino [5,6b] indole derivatives 104(a-o) followed by the reaction with Newly synthesized compounds 105(a-o) were screened for inhibitory activity against human (h) isoforms of CA, hCA I, II, XIII (cytosolic isoforms), and hCA IX (tumor related isoform) by the stopped-flow CO 2 hydrase assay method by taking AAZ as standard drug and it was observed that 105i (X = F, R = -CH (CH 3 ) 2 ) was found to show potent activity against hCA II and hCA XIII with K i values of 7.7 and 34.9 nM, respectively, as compared to AAZ (K i = 12.1 nM) due to the presence of fluoro-group at fifth position of indole moiety and isopropyl group attached to nitrogen of indole ring [34] (Scheme 15). (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129).…”

“…Sapegin et al reported a method to synthesize sulfonamide derivatives having new [1,4]oxazepines 1172(a-h) and 1175(a-d).…”

“…Initially, substituted isatins 872(a-c) were treated with alkyl halide, KI, and K 2 CO 3 in the presence of DMF to prepare N-alkylated isatin derivatives 874(a-o) followed by the reaction with thiosemicarbazide, 1,4-dioxane, and Cs 2 CO 3 to produce N-alkylated triazino[5,6-b] indolethioether derivatives 875(a-o). Second, compounds 875(a-o) were reacted with propargyl bromide, K 2 CO 3 in the presence of DMF at r.t. to prepare (N-Alkylated-3-prop-2-yn-1-ylthio)-5H-[1,2,4] triazino[5,6b]indole derivatives 876(a-o) which was further treated with CuSO 4 •5H 2 O and sodium ascorbate in presence of tBuOH: H 2 O at 60°C to obtain desired compounds 877(a-o).…”

Different spectrophotometric and TLC-densitometric methods for determination of olmesartan medoxomil and hydrochlorothiazide and their degradation products

“…After reviewing the literature extensively, different methods have been published for the determination of OLM and HCZ in their mixture. The binary mixture was analyzed by differrent spectrophotometric [6][7][8][9][10][11][12], spectrofluorimetric [13], electrophoretic [14], HPTLC [15][16][17][18], HPLC [15,[19][20][21][22][23][24][25][26][27][28][29][30][31], and UPLC [32,33] methods. The studied mixture was also determined in plasma by LC-MS [34][35][36].…”