Displaying publications 81 - 100 of 140 in total

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  1. Keck CM
    Int J Pharm, 2010 May 5;390(1):3-12.
    PMID: 19733647 DOI: 10.1016/j.ijpharm.2009.08.042
    The influence of optical parameters, additional techniques (e.g. PIDS technology) and the importance of light microscopy were investigated by comparing laser diffraction data obtained via the conventional method and an optimized analysis method. Also the influence of a possible dissolution of nanocrystals during a measurement on the size result obtained was assessed in this study. The results reveal that dissolution occurs if unsaturated medium or microparticle saturated medium is used for the measurements. The dissolution is erratic and the results are not reproducible. Dissolution can be overcome by saturating the measuring medium prior to the measurement. If nanocrystals are analysed the dispersion medium should be saturated with the nanocrystals, because the solubility is higher than for coarse micro-sized drug material. The importance of using the optimized analysis method was proven by analysing 40 different nanosuspensions via the conventional versus the optimized sizing method. There was no large difference in the results obtained for the 40 nanosuspensions using the conventional method. This would have led to the conclusion, that all the 40 formulations investigated are physically stable. However, the analysis via the optimized method revealed that from 40 formulations investigated only four were physically stable. In conclusion an optimized analysis saves time and money and avoids misleading developments, because discrimination between "stable" and "unstable" can be done reliably at a very early stage of the development.
    Matched MeSH terms: Drug Stability
  2. Jain A, Sharma G, Kushwah V, Garg NK, Kesharwani P, Ghoshal G, et al.
    Nanomedicine (Lond), 2017 Aug;12(15):1851-1872.
    PMID: 28703643 DOI: 10.2217/nnm-2017-0011
    AIM: This work was intended to investigate the targeting potential of fructose-tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find out the possible protective role of BC on MTX-induced toxicity.

    MATERIALS & METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied.

    RESULTS & CONCLUSION: Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.

    Matched MeSH terms: Drug Stability
  3. Rezaee M, Basri M, Rahman RN, Salleh AB, Chaibakhsh N, Karjiban RA
    Int J Nanomedicine, 2014;9:539-48.
    PMID: 24531324 DOI: 10.2147/IJN.S49616
    Response surface methodology was employed to study the effect of formulation composition variables, water content (60%-80%, w/w) and oil and surfactant (O/S) ratio (0.17-1.33), as well as high-shear emulsification conditions, mixing rate (300-3,000 rpm) and mixing time (5-30 minutes) on the properties of sodium diclofenac-loaded palm kernel oil esters-nanoemulsions. The two response variables were droplet size and viscosity. Optimization of the conditions according to the four variables was performed for preparation of the nanoemulsions with the minimum values of particle size and viscosity. The results showed that the experimental data could be sufficiently fitted into a third-order polynomial model with multiple regression coefficients (R(2) ) of 0.938 and 0.994 for the particle size and viscosity, respectively. Water content, O/S ratio and mixing time, quadrics of all independent variables, interaction between O/S ratio and mixing rate and between mixing time and rate, as well as cubic term of water content had a significant effect (P<0.05) on the particle size of nanoemulsions. The linear effect of all independent variables, quadrics of water content and O/S ratio, interaction of water content and O/S ratio, as well as cubic term of water content and O/S ratio had significant effects (P<0.05) on the viscosity of all nanoemulsions. The optimum conditions for preparation of sodium diclofenac nanoemulsions were predicted to be: 71.36% water content; 0.69 O/S ratio; 950 rpm mixing rate, and 5 minute mixing time. The optimized formulation showed good storage stability in different temperatures.
    Matched MeSH terms: Drug Stability
  4. Izadiyan Z, Basri M, Fard Masoumi HR, Abedi Karjiban R, Salim N, Kalantari K
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:841-849.
    PMID: 30423770 DOI: 10.1016/j.msec.2018.10.015
    Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).
    Matched MeSH terms: Drug Stability
  5. Shah SM, Ullah F, Khan S, Shah SM, de Matas M, Hussain Z, et al.
    Drug Des Devel Ther, 2016;10:3837-3850.
    PMID: 27920499
    Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena(®) DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.
    Matched MeSH terms: Drug Stability
  6. Azizi S, Ahmad MB, Hussein MZ, Ibrahim NA
    Molecules, 2013 May 28;18(6):6269-80.
    PMID: 23760028 DOI: 10.3390/molecules18066269
    Synthesis of ZnO-Ag heterostructure nanoparticles was carried out by a precipitation method with cellulose nanocrystals (CNCs) as a stabilizer for antimicrobial and thermal studies. ZnO-Ag nanoparticles were obtained from various weight percentages of added AgNO₃ relative to Zn precursors for evaluating the best composition with enhanced functional properties. The ZnO-Ag/CNCs samples were characterized systematically by TEM, XRD, UV, TGA and DTG. From the TEM studies we observed that ZnO-Ag heterostructure nanoparticles have spherical shapes with size diameters in a 9-35 nm range. The antibacterial activities of samples were assessed against the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The CNC-stabilized ZnO-Ag exhibited greater bactericidal activity compared to cellulose-free ZnO-Ag heterostructure nanoparticles of the same particle size. The incorporation of ZnO-Ag hetreostructure nanoparticles significantly increased the thermal stability of cellulose nanocrystals.
    Matched MeSH terms: Drug Stability
  7. Ali MA, Islam MA, Othman NH, Noor AM, Ibrahim M
    Acta Sci Pol Technol Aliment, 2020 1 14;18(4):427-438.
    PMID: 31930793 DOI: 10.17306/J.AFS.0694
    BACKGROUND: Rice bran oil (RBO) contains significant amounts of micronutrients (oryzanol, tocotrienol, tocopherol, phytosterols etc.) that impart a high resistance to thermal oxidation of the oil. The high oxidative stability of RBO can make it a preferred oil to improve the oxidative and flavor stabilities of other oils rich in PUFAs. In this study, the changes in the oxidative status and fatty acid composition in soybean oil (SO) blended with RBO under extreme thermal conditions were evaluated.

    METHODS: The blends were prepared in a volume ratio of 10:90, 20:80, 40:60, and 60:40 (RBO:SO). The changes in the oxidative parameters and fatty acid composition of the samples during heating at frying temperature (170°C) were determined using analytical and instrumental methods. Oxidative alteration was also monitored by recording FTIR spectra of oil samples.

    RESULTS: The increase in oxidative parameters (free fatty acid, color, specific extinctions, peroxide value, p-anisidine value, and thiobarbituric acid value) was greater in pure SO as compared to RBO or blend oils during heating. This indicates that the SO samples incorporated with RBO have the least degradation, while pure SO has the highest. Blending resulted in a lower level of polyunsaturated fatty acids (PUFA)  with       a higher level of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA). During heating, the relative content of PUFA decreased and that of SFA increased. However, the presence of RBO in SO slowed down the oxidative deterioration of PUFA. In FTIR, the peak intensities in SO were markedly changed in comparison with blend oils during heating. The reduction in the formation of oxidative products in SO during thermal treatment increased as the concentration of the RBO in SO increased; however, the levels of the protective effect of RBO did not increase steadily with an increase in its concentration.

    CONCLUSIONS: During thermal treatment, the generation of hydroperoxides, their degradation and formation of secondary oxidative products as evaluated by oxidative indices, fatty acids and IR absorbances were lower in blend oils compared to pure SO. In conclusion, RBO can significantly retard the process of lipid peroxidation in SO during heating at frying temperature.

    Matched MeSH terms: Drug Stability
  8. Masarudin MJ, Yusoff K, Rahim RA, Hussein MZ
    Nanotechnology, 2009 Jan 28;20(4):045602.
    PMID: 19417322 DOI: 10.1088/0957-4484/20/4/045602
    The delivery of a full plasmid, encoding the green fluorescent protein gene into African monkey kidney (Vero3) cells, was successfully achieved using nanobiocomposites based on layered double hydroxides. This demonstrated the potential of using the system as an alternative DNA delivery vector. Intercalation of the circular plasmid DNA, pEGFP-N2, into Mg/Al-NO(3)(-) layered double hydroxides (LDH) was accomplished through anion exchange routes to form the nanobiocomposite material. The host was previously synthesized at the Mg(2+) to Al(3+) molar ratio R(i) = 2 and subsequently intercalated with plasmid DNA. Size expansion of the interlamellae host from 8.8 A in LDH to 42 A was observed in the resulting nanobiocomposite, indicating stable hybridization of the plasmid DNA. The powder x-ray diffraction (PXRD) results, supplemented with Fourier-transform infrared (FTIR) spectroscopy, compositional and electrophoresis studies confirmed the encapsulation episode of the biomaterial. In order to elucidate the use of this resulting nanobiocomposite as a delivery vector, an MTT assay was performed to determine any cytotoxic effects of the host towards cells. The intercalated pEGFP-N2 anion was later successfully recovered through acidification with HNO(3) after treatment with DNA-degrading enzymes, thus also showing the ability of the LDH host to protect the intercalated biomaterial from degradation. Cell transfection studies on Vero3 cells were then performed, where cells transfected with the nanobiocomposite exhibited fluorescence as early as 12 h post-treatment compared to naked delivery of the plasmid itself.
    Matched MeSH terms: Drug Stability
  9. Hameed HA, Khan S, Shahid M, Ullah R, Bari A, Ali SS, et al.
    Drug Des Devel Ther, 2020;14:27-41.
    PMID: 32021089 DOI: 10.2147/DDDT.S232111
    BACKGROUND: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers.

    PURPOSE OF THE STUDY: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability.

    MATERIALS AND METHODS: NP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation.

    RESULTS: The hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3-74.31 ± 17.7 μm with Span index values of 0.491-0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent "n" value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (-3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed.

    CONCLUSION: The current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.

    Matched MeSH terms: Drug Stability
  10. Wong TW, Chan LW, Kho SB, Heng PW
    J Control Release, 2005 Jun 2;104(3):461-75.
    PMID: 15911046
    The influence of microwave irradiation on the drug release properties of freshly prepared and aged alginate, alginate-chitosan and chitosan beads was investigated. The beads were prepared by extrusion method with sulphathiazole as a model drug. The dried beads were subjected to microwave irradiation at 80 W for 10 min, 20 min or three consecutive cycles of 10 and 20 min, respectively. The profiles of drug dissolution, drug content, drug stability, drug polymorphism, drug-polymer interaction, polymer crosslinkage and complexation were determined by dissolution testing, drug content assay, differential scanning calorimetry and Fourier transform infra-red spectroscopy. The chemical stability of drug embedded in beads was unaffected by microwave conditions and length of storage time. The release property of drug was mainly governed by the extent of polymer interaction in beads. The aged alginate beads required intermittent cycles of microwave irradiation to induce drug release retarding effect in contrast to their freshly prepared samples. Unlike the alginate beads, the level of polymer interaction was higher in aged alginate-chitosan beads than the corresponding fresh beads. The drug release retarding property of aged alginate-chitosan beads could be significantly enhanced through subjecting the beads to microwave irradiation for 10 min. No further change in drug release from these beads was observed beyond 30 min of microwave irradiation. Unlike beads containing alginate, the rate and extent of drug released from the aged chitosan beads were higher upon treatment by microwave in spite of the higher degree of polymer interaction shown by the latter on prolonged storage. The observation suggested that the response of polymer matrix to microwave irradiation in induction of drug release retarding property was largely affected by the molecular arrangement of the polymer chains.
    Matched MeSH terms: Drug Stability
  11. Marrakchi F, Khanday WA, Asif M, Hameed BH
    Int J Biol Macromol, 2016 Dec;93(Pt A):1231-1239.
    PMID: 27663552 DOI: 10.1016/j.ijbiomac.2016.09.069
    Cross-linked chitosan/sepiolite composite was prepared from sepiolite clay and chitosan, and was cross-linked using epichlorohydrin. Among the various weight ratio percentage of chitosan and sepiolite clay composites, CS50SP50 was selected as the best adsorbent for both methylene blue (MB) and reactive orange 16 (RO 16). At an optimum adsorbent dosage of 0.2g/100mL, the effects of initial dye concentration (25-400mg/L) and pH (3-11) on MB and RO 16 adsorption onto CS50SP50 composite were studied. Monolayer adsorption capacities of CS50SP50 composite for MB and RO 16 were 40.986mg/g and 190.965mg/g, respectively at 30°C. Freundlich, Langmuir and Temkin isotherms applied on the adsorption data for both the dyes reveal that data fitted best for Freundlich model. For both the dyes pseudo-second-order kinetics were found to describe the adsorption process better than pseudo-first-order kinetics. The adsorption capacity of CS50SP50 composite for both the dyes was found better compared to previous studies thus making it potentially low-cost adsorbent for removal of both cationic and reactive dyes.
    Matched MeSH terms: Drug Stability
  12. Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN
    Int J Nanomedicine, 2012;7:2129-41.
    PMID: 22619549 DOI: 10.2147/IJN.S30461
    The intercalation of perindopril erbumine into Zn/Al-NO(3)-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.
    Matched MeSH terms: Drug Stability
  13. Hussein MZ, Al Ali SH, Zainal Z, Hakim MN
    Int J Nanomedicine, 2011;6:1373-83.
    PMID: 21796241 DOI: 10.2147/IJN.S21567
    An ellagic acid (EA)-zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8' position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host-guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.
    Matched MeSH terms: Drug Stability
  14. Ketuly KA, Hadi AH
    Molecules, 2010 Apr;15(4):2347-56.
    PMID: 20428047 DOI: 10.3390/molecules15042347
    Benzeneboronate of catecholic carboxyl methyl esters, N-acetyldopamine, coumarin and catechol estrogens were prepared as crystalline derivatives in high yield. Related catechol compounds with extra polar functional group(s) (OH, NH2) do not form or only partially form unstable cyclic boronate derivatives.
    Matched MeSH terms: Drug Stability
  15. Ramli NAS, Mohd Noor MA, Musa H, Ghazali R
    J Sci Food Agric, 2018 Jul;98(9):3351-3362.
    PMID: 29250790 DOI: 10.1002/jsfa.8839
    BACKGROUND: Palm oil is one of the major oils and fats produced and traded worldwide. The value of palm oil products is mainly influenced by their quality. According to ISO 17025:2005, accredited laboratories require a quality control procedure with respect to monitoring the validity of tests for determination of quality parameters. This includes the regular use of internal quality control using secondary reference materials. Unfortunately, palm oil reference materials are not currently available. To establish internal quality control samples, the stability of quality parameters needs to be evaluated.

    RESULTS: In the present study, the stability of quality parameters for palm oil products was examined over 10 months at low temperature storage (6 ± 2 °C). The palm oil products tested included crude palm oil (CPO); refined, bleached and deodorized (RBD) palm oil (RBDPO); RBD palm olein (RBDPOo); and RBD palm stearin (RBDPS). The quality parameters of the oils [i.e. moisture content, free fatty acid content (FFA), iodine value (IV), fatty acids composition (FAC) and slip melting point (SMP)] were determined prior to and throughout the storage period. The moisture, FFA, IV, FAC and SMP for palm oil products changed significantly (P  0.05). The stability study indicated that the quality of the palm oil products was stable within the specified limits throughout the storage period at low temperature.

    CONCLUSION: The storage conditions preserved the quality of palm oil products throughout the storage period. These findings qualify the use of the palm oil products CPO, RBDPO, RBDPOo and RBDPS as control samples in the validation of test results. © 2017 Society of Chemical Industry.

    Matched MeSH terms: Drug Stability
  16. Ruzilawati AB, Wahab MS, Imran A, Ismail Z, Gan SH
    J Pharm Biomed Anal, 2007 Apr 11;43(5):1831-5.
    PMID: 17240100
    In this study, the development and validation of a high-performance liquid chromatography (HPLC) assay for determination of repaglinide concentration in human plasma for pharmacokinetic studies is described. Plasma samples containing repaglinide and an internal standard, indomethacin were extracted with ethylacetate at pH 7.4. The recovery of repaglinide was 92%+/-55.31. Chromatographic separations were performed on Purospher STAR C-18 analytical column (4.8 mm x 150 mm; 5 microm particle size). The mobile phase composed of acetonitrile-ammonium formate (pH 2.7; 0.01 M) (60:40, v/v). The flow rate was 1 ml/min. The retention time for repaglinide and indomethacin were approximately 6.2 and 5.3 min, respectively. Calibration curves of repaglinide were linear in the concentration range of 20-200 ng/ml in plasma. The limits of detection and quantification were 10 ng/ml and 20 ng/ml, respectively. The inter-day precision was from 5.21 to 11.84% and the intra-day precision ranged from 3.90 to 6.67%. The inter-day accuracy ranged 89.95 to 105.75% and intra-day accuracy ranged from 92.37 to 104.66%. This method was applied to determine repaglinide concentration in human plasma samples for a pharmacokinetic study.
    Matched MeSH terms: Drug Stability
  17. Tan KL, Ankathil R, Gan SH
    J Chromatogr B Analyt Technol Biomed Life Sci, 2011 Nov 15;879(30):3583-91.
    PMID: 22000961 DOI: 10.1016/j.jchromb.2011.09.048
    We developed a simple and sensitive method for the simultaneous detection of imatinib mesylate (IM) and its active metabolite, N-desmethyl imatinib (M1), in human serum samples. Separation was successfully achieved using an Agilent(®) ZORBAX Eclipse plus C(18) reversed phase column (50 mm × 2.1 mm, i.d.; 1.8 μm) under isocratic mobile phase conditions consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate with 0.2% triethylamine at pH 3 (25:75, v/v) and ultra-violet detection was achieved at 235 nm. Extraction of the target compounds was completed using 100% cold acetonitrile. Good linearities (r(2)>0.99) for both IM and M1 were achieved for the concentration ranges of 50-1800 ng/mL and 50-360 ng/mL, respectively. The detection limits were 20 ng/mL and 10 ng/mL for M1 and IM, respectively. The intra- and inter-day precisions were less than 1% with percent recoveries of more than 90%. The method was successfully applied to calculate the pharmacokinetic parameters of chronic myeloid leukemia patients receiving imatinib. The method is suitable to be routinely applied for determination of IM and M1 in serum.
    Matched MeSH terms: Drug Stability
  18. Liew KB, Peh KK, Fung Tan YT
    Pak J Pharm Sci, 2013 Sep;26(5):961-6.
    PMID: 24035953
    An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.
    Matched MeSH terms: Drug Stability
  19. Gazzali AM, Lobry M, Colombeau L, Acherar S, Azaïs H, Mordon S, et al.
    Eur J Pharm Sci, 2016 Oct 10;93:419-30.
    PMID: 27575880 DOI: 10.1016/j.ejps.2016.08.045
    Folic acid is a small molecule, also known as vitamin B9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O2etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies.
    Matched MeSH terms: Drug Stability
  20. Siram K, Divakar S, Raghavan CV, Marslin G, Rahman H, Franklin G
    Colloids Surf B Biointerfaces, 2019 Feb 01;174:443-450.
    PMID: 30497005 DOI: 10.1016/j.colsurfb.2018.11.033
    The physico-chemical properties of lipids influencing the solubilisation of imatinib mesylate (IM) in lipid matrix were evaluated and a statistical model to predict the same has been derived in the present study. After experimental quantification of IM solubility in various lipids, Hansen Hildebrand's total solubility parameters were calculated in order to study the role of various forces connected to lipid-drug interaction. To develop a relationship between the various descriptors of the lipids and experimental solubility of IM in lipids (% w/w), quantitative structure-solubility relationship (QSSR) was used. To generate equations that can predict the solubility of IM in lipids (%w/w), multiple linear regression was used. Amongst the various lipids tested, glyceryl monostearate and behenic acid solubilised the highest (6.19 ± 0.22%) and lowest (0.01 ± 0.01%) amounts of IM respectively. Our results suggested that alkyl chain length, polarity of the lipids, index of cohesive interaction in solids, estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution, estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution and solvent accessible surface area collectively play a significant role in solubilising IM in the lipids. The equation developed could predict the solubility of IM in lipids with good accuracy (R2pred = 0.912).
    Matched MeSH terms: Drug Stability
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