Bioavailability Enhancement; Oral controlled drug delivery systems, Targeted drug delivery systems
15
Scopus Publications
Scopus Publications
Quality by Design approach for Optimization and Development of Cyclodextrin-Surfactant Complex Based Formulations for Bioavailability Enhancement of Valsartan Lakshmanarao Potti, Prameela Rani Avula, G Srikar, A Rani, C Sindhi, et al. Biointerface Research in Applied Chemistry, 2023 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.
Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability Uday Kumar THUMMALA, Eswar Gupta MADDI, Prameela Rani AVULA Journal of Research in Pharmacy, 2023 : 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.
Enhancement of Liver Targetability through Statistical Optimization and Surface Modification of Biodegradable Nanocapsules Loaded with Lamivudine Srikar Grandhi, Moawia Al-Tabakha, Prameela Rani Avula Advances in Pharmacological and Pharmaceutical Sciences, 2023 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.
Formulation Development and Evaluation of Once Daily Fexofenadine Hydrochloride Microsponge Tablets Ramani Gade, Sreekanth Nama, Prameela Rani Avula Trends in Sciences, 2023 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
Optimization of Fast-dissolving Tablets of Ledipasvir-sofosbuvir Inclusion Complexes by Design of Experiments Uday Kumar Thummala, Eswar Gupta Maddi, Prameela Rani Avula Indian Journal of Pharmaceutical Education and Research, 2023 Abstract: Background: Fast-dissolving tablets (FDTs) were aimed to be developed for the latest approved combination drugs for Hepatitis-C treatment, Ledipasvir (LDV) and sofosbuvir (SBV) which suffered with poor water solubility. Materials and Methods: Cyclodextrin (CD) complexation was done for the drugs to improve their solubility. The optimized CD complexes were taken for developing FDTs to improve dissolution limited bioavailability of these drugs. FDTs were developed by adopting design of experiments approach using Design Expert software. Type of β-CD, type of disintegrant and concentration of disintegrant were taken as the factors. Disintegration time, time for 90% dissolution of LDV and SBV were taken as the responses. The prepared tablets as per the selected experimental design were evaluated for the responses and also other characteristics like tensile strength, packing fraction, wettability. The results were analyzed by ANOVA and numerical optimization was performed with the desirability of minimizing all the responses. Results: All the selected factors were found to influence disintegration and dissolution times significantly. Dimethyl β-CD, croscarmellose sodium at 8% w/w was obtained as the optimized combination of the factors for the FDTs. The FTDs at this optimized combination of the factors were found to have 79.6 sec of DT, 17.72 and 13.68 min. of time for 90% dissolution of LDV and SBV respectively. Conclusion: These results which were significantly much better than those of the marketed tablets indicated that the FTDs were successfully developed using Design of experiments. Keywords: Fast dissolving tablets, Hepatitis-C, Ledipasvir, Sofosbuvir, Optimization.
Orodispersible tablets of telmisartan through cyclodextrin-surfactant complexation: A quality by design approach Lakshmanarao POTTI, Prameela Rani AVULA Journal of Research in Pharmacy, 2022 Telmisartan is a poorly water-soluble drug with dissolution limited bioavailability. In this work,solubility and dissolution rate were aimed to improve through the development of cyclodextrin (CD)complexes containing surfactant; followed by developing them into orodispersible tablets (ODTs). Qualityby design approach was adopted in the optimization of CD-surfactant complex as well as in the optimizationof ODTs. Type of cyclodextrins, the concentration of the cyclodextrins, and concentration of poloxamer 188were taken as the factors in the preparation of inclusion complexes by solvent evaporation method.Solubility was taken as the response variable. The optimized formulation of the complex was taken for ODTspreparation. Concentration of povidone, concentration of super-disintegrant and type of super-disintegrantwere taken as the independent factors, and disintegration time (DT) and time for 90% dissolution (T90%)were taken as the responses. The tablets were prepared by direct compression technique. The results of boththe responses were analyzed by response surface quadratic model for the influence of the factors on them.All three factors were found to have significant influence on both the responses (at p < 0.05). Graphicaloptimization was performed by desirability functions approach in order to have low DT and low T90%. Theoptimized telmisartan CD-surfactant complex was found to have a solubility of 2.86 mg/mL. The optimizedODTs were found to have 20.4 sec. DT and 7.3 min. T90%. These results indicated that enhancement ofsolubility of telmisartan as well as dissolution of the ODTs was successfully improved through quality bydesign approach.
Antiasthmatic activity of 2-piperidone by selective animal models Vani MAMILLAPALLI, Abdul Rahaman SHAIK, Prameela Rani AVULA Journal of Research in Pharmacy, 2020 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.
Hepatoprotective activity of 2-piperidone isolated from leaf extracts of Talinum portulacifolium (Forssk.) Asch. Ex Schweinf in carbon tetrachloride induced hepatotoxicity Vani Mamillapalli, Abdul Rahaman Shaik, Prameela Rani Avula Journal of Pharmacy and Pharmacognosy Research, 2019 Context: Liver disorders have become a common problem worldwide. The drugs available currently for the treatment are few with serious side effects. Since phytochemicals have proven to be potential therapeutic agents, an attempt has been made to screen novel hepatoprotective agents from the leaves of the medicinally ignored plant Talinum portulacifolium. Aims: To evaluate the phytoconstituents of Talinum portulacifolium responsible for hepatoprotective activity in carbon tetrachloride-induced hepatotoxicity models both in vitro and in vivo. Methods: The hepatic damage was assessed in vitro by serum marker enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase followed by in vivo histopathological examination. Results: The results of the study indicate that the plant hydroalcoholic and acetone extracts at 500 mg/kg and compound 2-piperidone at 0.5 mg/kg exhibited equipotent results in the reduction of biochemical marker enzymes (p<0.01. p<0.05 and p<0.001) significantly compared to standard drug silymarin. The histopathological studies further supported that compound 2-piperidone showed better regeneration of damaged hepatocytes compared to standard. The possible mechanism of action may be due to inhibition of cytochrome P450 2E induced endoplasmic reticulum and oxidative stress. Conclusions: The present study reveals that the hepatoprotective activity of leaf hydroalcoholic and acetone extracts may be due to the presence of 2-piperidone. As it showed equipotent potential to standard drug silymarin, it can be further developed as a hepatoprotective drug.
Development and validation of a lc-esi-ms/ms based bioanalytical method for dapagliflozin and saxagliptin in human plasma Swapna Goday, Abdul Rahaman Shaik, Prameelarani Avula Indian Journal of Pharmaceutical Education and Research, 2018 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.
Embedment technique: An alternative to wet granulation for better control of release of highly water soluble drugs–a case study with diltiazem HCl International Journal of Pharmacy and Pharmaceutical Sciences, 2015
