Avula Prameela Rani
@nagarjunauniversity.ac.in
Principal, Pharmacy
Acharya Nagarjuna University
EDUCATION
M. Pharmacy and Ph.D.
RESEARCH INTERESTS
Bioavailability Enhancement; Oral controlled drug delivery systems, Targeted drug delivery systems
Scopus Publications
Scopus Publications
Srikar Grandhi, Moawia Al-Tabakha, and Prameela Rani Avula
Hindawi Limited
The intention of the current work was to develop and optimize the formulation of biodegradable polymeric nanocapsules for lamivudine (LMV) in order to obtain desired physical characteristics so as to have improved liver targetability. Nanocapsules were prepared in this study as aqueous-core nanocapsules (ACNs) with poly(lactide-co-glycolide) using a modified multiple emulsion technique. LMV was taken as a model drug to investigate the potential of ACNs developed in this work in achieving the liver targetability. Three formulations factors were chosen and 33 factorial design was adopted. The selected formulation factors were optimized statistically so as to have the anticipated characteristics of the ACNs viz. maximum entrapment efficiency, minimum particle size, and less drug release rate constant. The optimized LMV-ACNs were found to have 71.54 ± 1.93% of entrapment efficiency and 288.36 ± 2.53 nm of particle size with zeta potential of −24.7 ± 1.2 mV and 0.095 ± 0.006 h−1 of release rate constant. This optimized formulation was subjected to surface modification by treating with sodium lauryl sulphate (SLS), which increased the zeta potential to a maximum of −41.6 ± 1.3 mV at a 6 mM concentration of SLS. The results of in vivo pharmacokinetics from blood and liver tissues indicated that hepatic bioavailability of LMV was increased from 13.78 ± 3.48 μg/mL ∗ h for LMV solution to 32.94 ± 5.12 μg/mL ∗ h for the optimized LMV-ACNs and to 54.91 ± 6.68 μg/mL ∗ h for the surface-modified LMV-ACNs.
Uday Kumar THUMMALA, Eswar Gupta MADDI, and Prameela Rani AVULA
ASOS Yayinevi
: The major goal of this research work was to augment bioavailability of the fixed-dose combination drugs, ledipasvir (LDV) and sofosbuvir (SBV) by developing orodispersible tablets and films and to estimate it by in vivo pharmacokinetic studies in rats. The pre-optimized amorphous solid dispersions of the LDV-SBV combination with HPMC E15 were made into orodispersible films (ODFs) and the pre-optimized inclusion complexes with dimethyl-β - cyclodextrin were made into orodispersible tablets (ODTs). The ODFs and ODTs were studied for the in vitro physical characterization studies and dissolution. Best of both the products were evaluated for in vivo pharmacokinetic studies in comparison with the marketed formulation of film coated tablets, Ledifos. The dissolution rate constants for the LDV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.269, 0.13 and 0.073 min.-1 respectively. The dissolution rate constants for the SBV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.302, 0.168 and 0.094 min.-1 respectively. Area under the curve (AUC) values for the LDV from the films, tablets and the marketed tablets were found to be 4231.4, 4050.3 and 3662.5 h*ng/mL respectively. AUC values for the SBV from the films, tablets and the marketed tablets were found to be 2173.2, 2084.6 and 1452.4 h*ng/mL respectively. Conclusion: The obtained results indicated that the optimized ODFs and the ODTs exhibited improved in vitro dissolution and in vivo bioavailability for the fixed-dose combination of LDV and SBV over the reference product.
Uday Kumar Thummala, Eswar Gupta Maddi, and Prameela Rani Avula
EManuscript Technologies
Ramani Gade, Sreekanth Nama, and Prameela Rani Avula
College of Graduate Studies, Walailak University
The objective of present study was to formulate and develop once daily Fexofenadine Hydrochloride tablets to improve the aqueous solubility by microsponge technology. Fexofenadine Hydrochloride is an antihistamine and belongs to BCS class-III with low permeability and poor bioavailability about 30 - 35 %. The microsponges were prepared by Quashi emulsion solvent diffusion method with Quality by design approach. The study of effect of independent variables Eudragit EPO (500 to 1,000 mg), internal phase volume (DM: ETH) (5 to 10 mL) and RPM (500 to 1,000) on responses were analyzed to optimize the formulation with desirable results by using central composite design and response surface method. Optimized formulation F22 showed percent production yield (99.10 %), percent drug entrapment (99.45 %), particle size (94.12 µm) and percent drug release of prepared tablets at 5, 10, 15 and 30 min were 60.6, 80.75, 87.47 and 92.85 %, respectively. It showed Higuchi mechanism of release kinetics by diffusion. In vivo pharmacokinetics of the prepared tablets was studied in rabbits (IAEC/NRML/2022–2023/09) with and without permeation enhancer to find the rate of absorption. when compared to Marketed product -Allegra 24 (F21) with (t1/2 absorption) 0.192711±0.00278 h and MRT 19.10608±0.257571 h and formulation without poloxamer 407 (F22) (t1/2 absorption) 0.165013±0.024164 h and MRT 19.32228±0.764531 h, maximum absorption was observed for the Formulation F23 with poloxamer 407 (15 %) with (t1/2 absorption) of 0.144662±0.006787 h and Mean residence time (MRT) of 24.10796±1.01232 h. Microsponge technique improved the aqueous solubility of the fexofenadine Hydrochloride and Eudragit EPO extended the mean residence time up to 24 h along with improved permeability in presence of Poloxamer 407 to full fill the needs of BCS class-III drug. HIGHLIGHTS Fexofenadine Hydrochloride has poor aqueous solubility and low passive permeability P-Glycoprotein efflux induced intestinal secretion is the reason for the incomplete absorption (35 %) following oral absorption There is a need to increase bioavailability and maintenance of steady state plasma concentration Microsponge drug delivery systems improvise the solubility of drug due to its porous nature Microsponge drug delivery system can fulfill the requirements by increasing the permeability and modifying the drug release from dosage form GRAPHICAL ABSTRACT
The main objective of the present research is to increase the oral bioavailability of Valsartan by inclusion complexes (ICVs) with a cyclodextrin-surfactant combination followed by the formulation of fast-dissolving tablets (FDTs). The solvent evaporation method was used for the preparation of ICVs. Methyl-ß-cyclodextrin and Hydroxypropyl-ß- cyclodextrin were evaluated with the combination of poloxamer 188 to get the formulations with the desired solubility. Central composite design (CCD) was used as the experimental design as a part of the quality by design (QbD) approach. The optimized ICVs were further developed into FDTs by direct compression technique. Taking concentration of povidone, type and concentration of disintegrant as the formulation factors, the FDTs were optimized using CCD. In-vivo bioavailability study in rats was performed for the optimized FDTs against the marketed tablets. The optimized ICVs were found to have a 3.12 mg/mL solubility. The optimized FDTs were found to be disintegrated in 18.7 sec and dissolved 90% of the dose in 6.3 min. The In-vivo results indicated that the FDTs exhibited rapid absorption and an increase in bioavailability by 24.1% against the marketed tablets. The results indicated that the QbD approach successfully improved Valsartan's oral bioavailability through cyclodextrin-surfactant complexation.
Ramani Gade, Sreekanth Nama, and Prameela Rani Avula
ASOS Yayinevi
Lakshmanarao POTTI and Prameela Rani AVULA
ASOS Yayinevi
Vani MAMILLAPALLI, Abdul Rahaman SHAIK, and Prameela Rani AVULA
ASOS Yayinevi
2-piperidone is a six membered heterocyclic compound existing naturally in piperaceae and portulaceae families. The synthetic derivatives of piperidone are promising bioactive molecules. They are antioxidant and antiinflammatory agents. Antihistaminic and anticholinergic studies are used as a part of antiasthmatic study. In the current study antihistaminic and anticholinergic studies were carried out using guinea pig bronchi and ilei in naturally isolated compound 2-piperidone from the plant Talinum portulacifolium. The results indicate that the compound (2 mg/kg 10.81 ± 1.29*** at p<0.001) showed profound antihistaminic activity significantly in histamine induced bronchospasm model than standard drug chlorpheniramine (2 mg/kg 8.77±0.43** at ** p<0.01). The compound can be further studied for antiasthmatic activity by various other ways to establish its mechanism of action as well as drug development studies to render it a novel antiasthmatic drug.
Swapna Goday, Abdul Rahaman Shaik, and Prameelarani Avula
EManuscript Technologies
Objective: To develop a new, rapid and sensitive LC-ESI –MS/MS method for the simultaneous estimation of Dapagliflozin and saxagliptin in human K2EDTA plasma by Liquid –liquid Extraction method (LLE) using deutereated dapagliflozin (DGd2) and saxagliptin (SGd5). Method: Chromatographic separation was carried out on a reverse phase hypersil Gold C 18 (50mmx3.0mm, 5μm) column using mixture of 10 mM Ammonium acetate and methanol (20:80, v/v) at a flow rate of 0.5ml/min in isocratic mode. Quantification was achieved using an electro spray ion interface operating in positive mode, under multiple reaction monitoring (MRM) conditions. Results: The method showed excellent linearity over the concentration range of 50.00-10000.00 pg/mL for both the analytes. The intrabatch and inter batch precision (%CV) was ≤4.5% and Matrix effect (%CV) was1.27%, 1.20% for both the analytes. Conclusion: The simplicity of the method allows for application in laboratories, presents a valuable tool for bioavailability, bioequivalence, pharmacokinetic studies.
Srikanth Inturi, Ratna Kumari Yejerla, Naga Suresh kumar Jujjuru, and Prameela Rani Avula
EManuscript Technologies
Objective: Venetoclax is a selective, potent, first-in-class BCL-2 inhibitor that restores apoptosis in cancer cells and has demonstrated clinical efficacy in a variety of haematological malignancies. There is no reported evidence for its measurement in human plasma. Method: A simple, sensitive and specific high-throughput HPLC-ESI-Tandem Mass Spectrometric method was developed for the estimation of Venetoclax (VX) in human plasma using Venetoclax-D8 (VXD8) as an internal standard (IS). Chromatographic separation was performed on Zorbax SB-C18, 75 x 4.6 mm, 3.5 mm, 80 A column with an isocratic mobile phase composed of Methanol and 5mM Ammonium acetate in the ratio of (70:30 v/v), at a flow-rate of 0.6 mL/min. The proton adducts of VX and VXD8 were detected at m/z 868.12 → 321.54 and 876.9 → 329.7 respectively, using multiple reaction monitoring (MRM) positive mode respectively. The Liquid-Liquid extraction method was used to extract the analyte and IS. Results: The method was successfully validated over linearity concentration range of 10.0-10000.0 pg/mL with the correlation coefficient (r 2 ) ≥ 0.9997. This method demonstrated intra and inter-day precision within 5.7 to 7.7 and 5.95 to 8.5 and % Accuracy within 96.3 to 98.7 and 98 to 100.4 %. Venetoclax was found to be stable throughout freeze-thawing cycles, bench top, postoperative stability studies. Conclusion: The method was suitable and conveniently applicable to pharmacokinetic and bioavailability studies for estimation of Venetoclax in biological matrices by HPLC-MS/MS. Key words: Deuterium, Pharmacokinetic, Plasma, Proton adduct, Venetoclax.
Srikanth Inturi and Prameela Rani Avula
FapUNIFESP (SciELO)
A simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of cabozantinib (CZ) in human plasma using cabozantinib-d4 (CZD4) as an internal standard (IS). Chromatographic separation was performed on Xbridge C18, 50 x 4.6 mm, 5 mm column with an isocratic mobile phase composed of 10mM Ammonium formate and Methanol in the ratio of (20:80 v/v), at a flow-rate of 0.7 mL/min. CZ and CZD4 were detected with proton adducts at m/z 502.2 → 391.1 and 506.3 → 391.2 in multiple reaction monitoring (MRM) positive mode respectively. Liquid-Liquid extraction method was used to extract the drug and IS. The method was validated over a linear concentration range of 5.0-5000.0 pg/mL with correlation coefficient (r2) ≥ 0.9994. This method demonstrated intra and inter-day precision within 1.95 to 2.37 and 2.93 to 9.3 % and Accuracy within 101.4 to 102.4 and 99.5 to 104.8 %. Cabozantinib was found to be stable throughout freeze-thawing cycles, bench top and postoperative stability studies.
Hema Veesam and PrameelaRani Avula
Siree Journals
Purpose: The aim of the present research is to monitor any alteration in the serum concentrations of lamotrigine (LMT) in peripheral neuropathic conditions compared with normal conditions in a rat model. Materials and Methods: LMT concentrations were established at 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h post dose by high performance liquid chromatography-ultraviolet. After per oral administration of 10 mg/kg drug, pharmacokinetic parameters were determined from plasma drug concentration. Later pharmacokinetic parameters of neuropathic pain induced rats were calculated in order to estimate the possible effect of neuropathic pain on pharmacokinetic parameters. Results: The regression coefficient determined for LMT calibration curve was 0.99 ± 0.001. The working range for LMT was 0.5 to 2.5 μg/ml Limit of Detection (LOD 0.2 μg/ml). The maximum drug concentration was found at 2 h. Conclusion: However, none of the pharmacokinetic parameter showed statistically significant alteration where the results were quite stimulating for the development of clinically useful oxcarbazepine dosage form to explore its activity on neuropathic pain.