Compatibility study between diazepam and tablet excipients

Published on Feb 1, 2017in Journal of Thermal Analysis and Calorimetry2.471
· DOI :10.1007/s10973-016-5350-9
A. P. S. Matos1
Estimated H-index: 1
(UFRJ: Federal University of Rio de Janeiro),
J. S. Costa1
Estimated H-index: 1
(FIOCRUZ: Oswaldo Cruz Foundation)
+ 5 AuthorsC. Holandino1
Estimated H-index: 1
(UFRJ: Federal University of Rio de Janeiro)
Compatibility between diazepam (DZP), a benzodiazepine drug used for the treatment of anxiety, and tablet excipients has been investigated by thermal analysis (differential scanning calorimetry—DSC and thermogravimetry—TG) and infrared (IR) spectroscopy. In order to investigate possible interactions, the components were prepared in 1:1 (w/w) mixtures. Moreover, individual samples as well as physical mixtures were stored in accelerated conditions at 40 °C/75 % RH for 3 months. Mixtures, which showed possible interactions, were also investigated in other ratios based on typical pharmaceutical solid formulation. DSC curves of DZP have shown an endothermic peak at 132 °C, which corresponds to the melting process in agreement with the literature. DSC curves of the mixtures containing DZP and colloidal silicon dioxide (CSD) indicated a possible interaction due to enthalpy values lower than expected. However, as this interaction was not confirmed by IR and TG, this suggests that these techniques are not sensitive enough to identify such interaction. These results suggest that there is a possible interaction, but not an incompatibility between DZP and CSD. For all other mixtures, it was not possible to identify significant interactions, suggesting that there are no compatibility issues.
  • References (26)
  • Citations (8)
📖 Papers frequently viewed together
9 Citations
24 Citations
1 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
The main objective of this work was to use the differential scanning calorimetry in conjunction with optical microscopy to study the compatibility of ibuprofen with lactose and polyvinylpyrrolidone and to provide an explanation(s) for the reduction in the dissolution rate observed from the ternary interactive mixture containing ibuprofen in previous study. Mixtures containing micronized ibuprofen–fine lactose 90:10 and 20:80 w/w showed a decrease in the melting peak of lactose by 14.33 and 10.94...
10 CitationsSource
Last. Ricardo Neves Marreto (UFG: Universidade Federal de Goiás)H-Index: 10
view all 10 authors...
Carvedilol (CARV) is a widely used non-selective β-blocker, which has shown low bioavailability after oral administration (20 %) due to its low water solubility and intense first-pass metabolism. Lipid-based drug delivery systems have been proposed to improve CARV oral bioavailability. An evaluation of drug–excipient compatibility is needed to clarify potential physical and chemical interactions between them and therefore guarantee a correct selection of excipients. However, to date there are no...
14 CitationsSource
The importance of developing new pharmaceutical final formulations is nowadays well known. In this paper, we present the study of compatibility between bioactive antihyperlipidemic agent simvastatin and eight currently used pharmaceutical excipients for developing solid dosage forms, namely starch, microcrystalline cellulose, lactose monohydrate, polyvinylpyrrolidone, colloidal silica, talc, magnesium citrate and sorbitol. The compatibility investigations were carried out under ambient temperatu...
10 CitationsSource
Differential scanning calorimetry (DSC) is a primary technique for measuring the thermal properties of materials, which reflects the physico-chemical properties of drug substances. In the present study, it is used as a screening technique for assessing the compatibility of sitagliptin with some currently employed pharmaceutical excipients. The influence of processing conditions and their effects (simple blending, co-grinding or kneading) on drug stability was evaluated. Sitagliptin showed a shar...
18 CitationsSource
#1Renu Chadha (Panjab University, Chandigarh)H-Index: 17
#2Swati Bhandari (Panjab University, Chandigarh)H-Index: 7
Abstract Estimation of drug–excipient interactions is a crucial step in preformulation studies of drug development to achieve consistent stability, bioavailability and manufacturability of solid dosage forms. The advent of thermoanalytical and spectroscopic methods like DSC, isothermal microcalorimetry, HSM, SEM, FT-IR, solid state NMR and PXRD into pre-formulation studies have contributed significantly to early prediction, monitoring and characterization of the active pharmaceutical ingredient ...
67 CitationsSource
Abstract Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques were used for assessing the compatibility between ketoprofen (KT) and several excipients as: corn starch, microcrystalline cellulose (PH 101 and PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone K30, magnesium stearate and talc, commonly used in the pharmaceutical form. In order to investigate the possible interactions between the compone...
80 CitationsSource
Abstract Different pharmaceutical preparations against the common cold containing phenylephrine (PHE) and saccharose were studied. New impurities were discovered in these preparations after exposure using isocratic ion-pair chromatography separation on a C18 column. LC–MS and NMR techniques were employed to identify and to fully characterize these new compounds. The products were identified as 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,8-diol and 1-[5-(hydroxymethyl)-...
15 CitationsSource
#1Karin Liltorp (Lundbeck)H-Index: 1
#2Trine Gorm Larsen (Lundbeck)H-Index: 1
Last. René Holm (Lundbeck)H-Index: 30
view all 4 authors...
Abstract Compatibility between two new active pharmaceutical ingredients (API) and several pharmaceutical excipients used in solid formulations has been investigated by FT-IR and HPLC following storage under two different conditions. Compatibility was investigated by storage at isothermal stress conditions for (i) 3 days and subsequently analysed by FT-IR and (ii) 12 weeks of storage and analysis by HPLC. For the majority of the examined excipients a large degradation measured by HPLC after 12 w...
40 CitationsSource
#1Jadwiga Mielcarek (Poznan University of Medical Sciences)H-Index: 17
#2D.M. Nowak (JINR: Joint Institute for Nuclear Research)H-Index: 1
Last. Jan WąsickiH-Index: 8
view all 5 authors...
Reorientation of the molecule of diazepam was investigated by calorimetric methods, IR absorption and NMR. The investigation of dynamics was complemented by density functional study (DFT) of vibrational frequencies and infrared intensities, calculations of steric hindrances and Monte Carlo simulations. The results indicated the occurrence of reorientation jumps of the CH3 group and conformational motion of the benzodiazepine ring. The activation parameters of the methyl group reorientation were ...
9 CitationsSource
#1Farnaz Monajjemzadeh (Tabriz University of Medical Sciences)H-Index: 8
#2Davoud Hassanzadeh (Tabriz University of Medical Sciences)H-Index: 8
Last. Michael S. Roberts (UniSA: University of South Australia)H-Index: 67
view all 7 authors...
Abstract This study documents drug–excipient incompatibility studies of acyclovir in physical mixtures with lactose and in different tablet brands. Differential scanning calorimetry (DSC) was initially used to assess compatibility of mixtures. The Fourier-transform infrared (FTIR) spectrum was also compared with the spectra of pure drug and excipient. Although DSC results indicated incompatibility with lactose, FTIR spectra were mostly unmodified due to overlapping peaks. Samples of isothermally...
42 CitationsSource
Cited By8
#1Nicole S. Jones (RTP: Research Triangle Park)
#2Jeffrey H. Comparin (Drug Enforcement Administration)
Abstract This review paper covers the forensic-relevant literature in controlled substances from 2016 to 2019 as a part of the 19th Interpol International Forensic Science Managers Symposium. The review papers are also available at the Interpol website at: .
AbstractEmpagliflozin (EGF) received USFDA approval in 2014 for oral use to control the glucose levels in adults with type 2 diabetes mellitus. Albeit, a systematic drug-excipient compatibility stu...
#1Ionuț LedețiH-Index: 1
#2Mirabela RomanescuH-Index: 1
Last. Doina PiciuH-Index: 5
view all 12 authors...
The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D...
1 CitationsSource
#1Mariana S. Lopes (Universidade Federal de Alfenas)H-Index: 1
#2Tiago A. Catelani (Universidade Federal de Alfenas)H-Index: 1
Last. Marcello G. Trevisan (Universidade Federal de Alfenas)H-Index: 12
view all 5 authors...
Ketoconazole (KTZ) is an antifungal agent responsible for the inhibition of 14-α-demethylase sterol. The drug–excipient compatibility studies play an important role in pharmaceutical formulations development. Interactions between drug and excipients may affect the chemical nature, stability, bioavailability and consequently the therapeutic efficacy and safety profile. The main goal of this work was to evaluate the compatibility of KTZ with some excipients: corn starch, microcrystalline cellulose...
3 CitationsSource
The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the her...
2 CitationsSource
#1Uroš Maver (University of Maribor)H-Index: 18
#2Marko Milojević (University of Maribor)H-Index: 1
Last. Odon Planinšek (University of Ljubljana)H-Index: 22
view all 5 authors...
Cost and time effectiveness make direct tableting still the favored method for tablet production. Among its most noticeable limitations in application is the non-uniformity (and/or inhomogeneities) in the contents of the resulting tablets, possibly leading to inconsistencies in required tablet properties. The efficiency of direct tableting is mostly affected by surface properties of the components to be tableted, which govern the final tablet mechanical and chemical properties and can influence ...
1 CitationsSource
#1María Ana Rosasco (UBA: University of Buenos Aires)H-Index: 5
#2Silvina L. Bonafede (UBA: University of Buenos Aires)H-Index: 1
Last. Adriana Ines Segall (UBA: University of Buenos Aires)H-Index: 11
view all 4 authors...
Differential scanning calorimetry (DSC), isothermal stress testing–Fourier transform infrared spectroscopy (IST–FTIR), isothermal stress testing–high-performance liquid chromatography, and powder X-ray diffraction (PDRX) were used as screening techniques for assessing the compatibility of tobramycin with some currently employed ophthalmic excipients. In the first phase of the study, DSC was used as a tool to detect any interaction. The absolute value of the difference between the enthalpy of the...
1 CitationsSource
#1József Magyari (University of Novi Sad)H-Index: 3
#2Berta Holló (University of Novi Sad)H-Index: 8
Last. Katalin Mészáros Szécsényi (University of Novi Sad)H-Index: 13
view all 11 authors...
There is a complex interplay between the structural and other physicochemical properties of new compounds and the molecules in living organisms. To understand the mechanism of the interactions at the molecular level, the correlations between the selected properties and their biological responses have to be examined. With this aim, in this paper, density functional theory (DFT) and LMP2 calculations were carried out for the 2-acetylpyridine-aminoguanidine ligand, L, and its copper(II) complexes c...
3 CitationsSource
#1Elionai Cassiana de Lima Gomes (UFMG: Universidade Federal de Minas Gerais)H-Index: 7
#2Izabella Ercole de Carvalho (UFMG: Universidade Federal de Minas Gerais)H-Index: 1
Last. Armando Silva-Cunha (UFMG: Universidade Federal de Minas Gerais)H-Index: 19
view all 6 authors...
Most of the pharmaceutical products are formulated as solid dosage form, which may present drug–excipient interactions that lead to changes in the chemical nature of the drug, such as solubility and bioavailability and may compromise its safety and effectiveness. Differential scanning calorimetry (DSC) is a widely used method for the rapid evaluation of the drug-excipient compatibility and the stability of the mixture formed; however, there is no consensus on the preparation methods of the drug–...
2 CitationsSource
Abstract Rufinamide (R) is a triazole derivative approved for the management of partial seizures and seizures associated with Lennox-Gastaut Syndrome, in November 2007. Crystal structure, solid state characterization, drug-excipient compatibility and solubility play a pivotal role in formulation development. This work deals with the crystal structure elucidation of R by single crystal X-ray diffraction and solid state characterization by thermal, spectroscopic and crystallographic techniques. Dr...
1 CitationsSource