Department of Pharaceutical Quality Assurance
Details of the publications of the department can be viewed at:
1. Mathew, Elizabeth Mary and Moorkoth, Sudheer and Rane, Pankaj D and Lewis, Leslie and Rao, Pragna (2019)
Chemical and Pharmaceutical Bulletin, 67 (2). pp. 88-95. ISSN 0009-2363
25-Hydroxyvitamin D (25-(OH)D) deficiency is recently been described as one of the multiple factors responsible for pediatric seizures. 25-Hydroxyvitamin D3 and 25- ydroxyvitamin D2 are the well-known markers to determine Vitamin D status. In this work we report the development of a sensitive and cost effective HPLC technique for the quantification of the vitamin D metabolites from dried blood spot samples (DBS). The metabolites were extracted using acetonitrile–methanol–0.1% formic acid 60 : 20 : 20 (v/v)) and analyzed on an Acclaim C18 column (150 × 4.6 mm i.d., 3 µm) at a flow rate of 1 mL/min. The method was linear in the range of 10–80 ng/mL. Limit of detection and limit of quantification (LOQ) of the method were 5 and 10 ng/mL respectively. Extensive stability studies demonstrated the analytes to be stable in stock and matrix with a percent change within the acceptable range of ±15%. Comparison of the newly developed HPLC-DBS method with the reported LC-MS-DBS and electrochemiluminescence immunoassay (ECLIA) methods followed by Bland–Altman analysis demonstrated a bias of 0.08 and −0.14, respectively proving the methods are comparable. Application of the developed method to a pediatric seizure cohort depicted 46.6% of cases as deficient and 26.6% as insufficient for 25-(OH)D. Among deficient cases 8 samples were below 10 ng/mL and exact amount was not calculated since these were below the LOQ levels. The mean ± standard deviation (S.D.) in the remaining 6 deficient cases was 13.22 ± 2.80 ng/mL. The levels in healthy infants were 33.9 ± 6.11 ng/mL. The method can be used routinely for assessing 25-(OH)D deficiency in newborn.
2. Mathew, Elizabeth Mary and Lewis, Leslie Edward Simon and Rao, Pragna and Nalini, K and Kamath, Asha and Moorkoth, Sudheer (2019)
Journal of Chromatographic Science, 57 (8). pp. 1-9. ISSN 0021-9665
Methyl malonic acid and branched-chain keto acids are important biomarkers for the diagnosis of cobalamin deficiencies and maple syrup urine disease. We report the development and validation of a HILIC-ESI-MS2 method for the quantification of these organic acids from neonatal urine. The samples were 100 times diluted and analyzed on a ZIC- ILIC column with 25-mM formic acid in water: 25-mM formic acid in acetonitrile (45:55) at a flow rate of 0.8 mL/min with a runtime of only 6 minutes. The method demonstrated a lower limit of detection of 10 ng/mL, Limit of Quantification (LOQ) of 50 ng/mL, linearity of r2 ≥ 0.990 and recoveries of 87–105% for all analytes.The intraday and interday precision CV’s were <10% and 12%, respectively. Extensive stability studies demonstrated the analytes to be stable in stock and in matrix with a percent change within ±15%. The Bland–Altman analysis of the developed method with the gold standard GCMS method demonstrated a bias of 0.44, 0.11, 0.009 and –0.19 for methyl malonic acid, 3-methyl-2-oxovaleric acid, 2- ydroxy-3methylbutyric acid and 4-methyl-2-oxovaleric acid, respectively, proving the methods are comparable. The newly developed method involves no derivatization and has a simple sample preparation and a low runtime, enabling it to be easily automated with a high sample throughput in a cost-effective manner
3. Gohel, SunilKumar V and Bhat, Krishnamurthy (2019)
Journal of Molecular Structure, 1178. pp. 479-490. ISSN 0022-2860
Supramolecular reactions between a muscle relaxant drug, Metaxalone, 5-[(3,5-dimethylphenoxy) methyl]-2-oxazolidinone with a few carboxamides like nicotinamide, isonicotinamide, salicylamide and carboxylic acid coformers such as 3- ydroxybenzoic acid, 4-hydroxybenzoic acid resulted binary coc- rystals. The cocrystals were initially characterized by PXRD, FT/IR, ss-NMR, DSC and finally confirmed by single crystal X-ray diffraction. Surprisingly, all the novel cocrystals exhibited melting endotherm lower than the drug and coformer, which is not so common (29%) in the literature. Vibrational spec- troscopy suggests the possible stoichiometry of the drug cocrystals based on the number of carbonyl stretching frequencies and hydrate formation in case of 4-hydroxybenzoic acid cocrystal. 13C-ssNMR spectroscopy of metaxaloneesalicylamide cocrystal indicates the possibility of more symmetry inde-pendent molecule of the drug in the starting material to less in the cocrystal and molecular conformation was also reflected in the spectrum. The corresponding crystal structure consists of one molecule each of metaxalone and salicylamide in the asymmetric unit. Similar to the thermodynamically stable form of the drug and cocrystals with mono/di-carboxylic acids, metaxalone forms centrosymmetric NeH/O hydrogen bonded imide-imide homodimer in this cocrystal. Salicylamide molecules also form centro-symmetric amide-amide homosynthon. Both the homodimers are perpendicularly (79!) interlinked via bifurcated carbonyl oxygen of the drug, which results 1D chain along the crystallographic b-axis.Auxiliary C/H/O interactions further stabilize the bonding between the drug and salicylamide. Binding energy calculation of metaxalone/salicylamide homodimer and metaxalone!salicylamide heterodimer using B3LYP/6-311þþG** method and in addition, the stacking energy interactions in the API suggest the most preferred API homodimer synthon in the reported polymorphs and cocrystals. The pharmaceutical cocrystals of metaxalone with amide functionalities are reported for the first time in the literature.
4. Lobo, Lonita and Dengale, Swapnil J (2018)
European Journal of Pharmaceutics and Biopharmaceutics, 132. pp. 192-199. ISSN 0939-6411
Liquid-assisted grinding (LAG) and dry ball milling (DBM) have recently been used to obtain different physical forms of drug-amino acid salts with promising dissolution and physical stability properties. In this work, crystalline and co-amorphous naproxen-arginine mixtures were prepared using LAG and DBM, respectively, and compared with regard to their in vitro and in vivo performance. X-ray powder diffraction and Fourier-transformed infrared spectroscopy showed that LAG led to the formation of a crystalline salt, while DBM led to a co-amorphous salt. These results agreed with the differential scanning calorimetry profiles: a melting point of 230 °C was determined for the crystalline salt, while the co-amorphous formulation showed a single glass transition temperature at approx. 92 °C. Both solid state forms of the salt showed increased intrinsic dissolution rates (14.8 and 74.1-fold, respectively) and also higher solubility (25.3 and 29.8-fold, respectively) compared to the pure crystalline drug in vitro. Subsequently, the co-amorphous salt revealed an improved bioavailability in a pharmacokinetic study, showing a 1.5-fold increase in AUC0-t and a 2.15-fold increase in cmax compared to the pure crystalline drug. In contrast, even though showing a better in vitro performance, the crystalline salt interestingly did not show an increase in bioavailability in comparison to pure crystalline naproxen.
5. Chamle, AH and Shane, NLJ and Pai, Aravinda and Muddukrishna, BS (2019)
Indian Journal of Pharmaceutical Sciences, 81 (1). pp. 57-62. ISSN 0250 - 474X
Methylcobalamin is a highly photolabile and unstable molecule and hence, studies regarding photodegradation of methylcobalamin were carried out. In order to investigate the stability studies, the drug was subjected to photodegradation by exposing it to different light conditions in the validated photostability chamber as per ICH Q1B guideline. The drug was found to be less degraded in the blue light and was more prone to degradation under fluorescent light. Validated stability indicating liquid chromatography method was used for separating the methylcobalamin and its degradation products. The methylcobalamin peak with a retention time of 2.978 min was observed to decrease with a commensurate increase in a degradant peak at 4 min. The observed degradant peak was suspected to be hydroxocobalamin and was further confirmed by molecular weight determination. The fractions collected from high performance liquid chromatography were later injected into mass detector to determine the mass of the degradation products, which was found to be 665.78 amu.
- Jadeja, Siddharth and Pai, Girish K and Muddukrishna, BS (2016) Adoption and reasons for withdrawal of ICH Q1F guidelines. Journal of Young Pharmacists, 8 (4). pp. 500-504. ISSN 0975-1483
- Mudgal, Jayesh and Gowdra, Vasantharaju S and Mudgal, Piya Paul and Nayak, Pawan G and Kumar, Nitesh and Attari, Zenab and Rao, Mallikarjuna C and Nampurath, Gopalan Kutty (2016) Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary lesions of polyarthritis: A multi-parametric approach. European Journal of Pharmaceutical Sciences, 91. pp. 74-83. ISSN 0928-0987
- Kumari, Ramya G and Deepika, NC and Bhat, Krishnamurthy (2016) Simultaneous estimation of emitricitabine, efavirenz, tenofovir disproxil fumarate by chemometry and reverse phase-high performance liquid chromatography. Indian Drugs, 53 (6). pp. 62-69. ISSN 0019-462X
- Attari, Zenab and Bhandari, Amita and Jagadish, PC and Lewis, Shaila (2016) Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology. Saudi Pharmaceutical Journal, 24 (1). pp. 57-63. ISSN 1319-0164.
- Simon, Lalitha and Srinivasan, KK and Kumar, Nitesh and Reddy, Neetinkumar D and Biswas, Subhankar and Rao, Mallikarjuna C and Moorkoth, Sudheer (2016) Selected novel 5’-amino-2’-hydroxy-1, 3-diaryl-2- propen-1-ones arrest cell cycle of hct-116 in g0/g1 phase. EXCLI Journal, 15 (1). pp. 21-32. ISSN 1611-2156.
- Medikonduri, Ushasree and Attari, Zenab and Bhat, Krishnamurthy and Lewis, Shaila (2016) Acyclovir Entrapped N-Trimethyl Chitosan Nanoparticles for Oral Bioavailability Enhancement. Current Nanoscience, 12 (3). pp. 378-385. ISSN 1573-4137.
- Dabir, Janhavi and Mathew, Elizabeth Mary and Moorkoth, Sudheer (2016) Analytical Method Development and Validation of RP-HPLC Method for Simultaneous Estimation of N-acetyl cysteine and Cefexime from its Fixed Dose Combination.Research Journal of Pharmacy and Technology, 9 (7). pp. 835-842. ISSN 0974-360X.
- Bhagawati, ST and Chonkar, Ankita D and Dengale, Swapnil J and Reddy, Sreenivasa M and Bhat, Krishnamurthy (2016)Bioavailability Enhancement of Rizatriptan Benzoate by Oral Disintegrating Strip: In vitro and In vivo Evaluation. Current Drug Delivery, 13 (3). pp. 462-470.
- Pawar, Chandrakant and Rao, Pragna and Lewis, Leslie and Moorkoth, Sudheer (2016) Development of a gc-ms Bio-analytical method to detect organic Acidemia in neonatal/ paediatric urine Sample. International Journal Of Pharmacy & Technology, 8 (2). pp. 13110-13124. ISSN 0975-766X.
- Chonkar, Ankita D and Rao, Venkata J and Managuli, Renuka S and Mutalik, Srinivas and Dengale, Swapnil J and Jain, Prateek and Udupa, N (2016) Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation. European Journal of Pharmaceutics and Biopharmaceutics, 103. pp. 179-191. ISSN 0939-6411.
- Bhandari, Amita and Attari, Zenab and Musmade, Prashant B and Lewis, Shaila (2016) Enhanced intestinal permeability of quercetin coated felodipine beads in wistar rats. Formulation and Ex vivo study. Latin American Journal of Pharmacy, 35 (3). pp. 558-563. ISSN 0326 2383.
- Dengale, Swapnil Jayant (2016) Recent Advances in Co-amorphous Drug Formulations. Advanced Drug Delivery Reviews, 100. pp. 116-125.
- Pai, Girish K and Muddukrishna, BS (2016) Stability indicating HPTLC determination of triamcinalone acetonide in bulk drug and sterile injectable suspension. Journal of Young Pharmacists, 8 (4). pp. 430-435. ISSN 0975-1483