Author(s):
Atul S. Gurav, Ajit S. Kulkarni
Email(s):
atulgurav800@gmail.com
DOI:
10.52711/0974-360X.2024.00034 
Address:
Atul S. Gurav1,2*, Ajit S. Kulkarni3
1Gourishankar Education Society's, Satara College of Pharmacy, Satara, MS, India.
2Late Adv. Dadasaheb Chavan Memorial Institute of Pharmacy, Masur, Karad, Satara, MS, India.
3Principal, Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara, MS, India.
*Corresponding Author
Published In:
Volume - 17,
Issue - 1,
Year - 2024
ABSTRACT:
The objective of this research was to improve the solubility and dissolution rate of Efavirenz (EFA), a BCS II drug utilized for HIV infection treatment, by cocrystallization with ascorbic acid (AA). An in silico analysis indicated that EFA and AA exhibited physical interaction and compatibility. EFA exists in two polymorphic forms, I and II, with varying crystalline habits, where polymorph II presents better solubility and dissolution rate. Cocrystals were prepared using the solvent evaporation method by varying AA concentration and temperature. FTIR and NMR analysis confirmed the absence of chemical interaction between EFA and AA. Increasing AA concentration and temperature significantly increased the saturation solubility. DSC, XRD and SEM analysis revealed a shift in the endothermic peak of EFA, change in intensity with 2? values, and modified surface morphology respectively. This also confirmed a polymorphic structure change in the cocrystals due to high heating rates and maximum crystallization rate. The dissolution rate of the cocrystals was enhanced by the optimized batch, which contained an intermediate concentration of AA and was subjected to the highest temperature condition, and the data fitted well with the Higuchi model of kinetics. The stability of the cocrystals was also evaluated by accelerated stability testing to determine the percentage of drug content. Thus, cocrystallization with AA proved to be a suitable approach for enhancing the dissolution characteristics and polymorphic modification of BCS II drugs, such as EFA.
Cite this article:
Atul S. Gurav, Ajit S. Kulkarni. Efavirenz cocrystals with Ascorbic acid: A Strategy for Polymorphic Modification and improvement of Dissolution properties. Research Journal of Pharmacy and Technology. 2024; 17(1):213-1. doi: 10.52711/0974-360X.2024.00034
Cite(Electronic):
Atul S. Gurav, Ajit S. Kulkarni. Efavirenz cocrystals with Ascorbic acid: A Strategy for Polymorphic Modification and improvement of Dissolution properties. Research Journal of Pharmacy and Technology. 2024; 17(1):213-1. doi: 10.52711/0974-360X.2024.00034 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-1-34
REFERENCES:
1. Aleti R, Murthy KV. Development and validation of UV spectroscopic method for estimation of sacubitril and valsartan combination (LCZ696) in bulk and pharmaceutical tablet dosage forms. Research Journal of Pharmacy and Technology. 2022; 15(11): 5232-8. DOI: 10.5271/0974-360X.2022.00881
2. Murugesan V, Sonali K, Vigneshwaran N. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): a brief overview of clinically approved drugs and combination regimens. Current Opinion in Pharmacology. 2020; (54): 179-87. DOI:10.1016/j.coph.2020.10.009
3. Shinde VR, Pore YV, Rao JV. A Novel Co-crystallization Technique to enhance the physicochemical property of BCS Class-II drugs using Efavirenz as a model drug. Research Journal of Pharmacy and Technology. 2022; 15(4): 1603-9. DOI: 10.52711/0974-360X.2022.00268
4. Sankaraiah J, Sharma N, Naim MJ. Formulation And Development Of Fixed-Dose Combination Of Bi-Layer Tablets Of Efavirenz, Lamivudine And Tenofovir Disoproxil Fumarate Tablets 600 Mg/300 Mg/300 Mg. Int J App Pharm. 2022; 14(1): 185-97. DOI: https://dx.doi.org/10.22159/ijap.2022v14i1.42764.
5. Yadav, D., Savjani, J., Savjani, K. et al. Pharmaceutical Co-crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability. AAPS Pharm Sci Tech. 2023; 24(7). https://doi.org/10.1208/s12249-022-02467-7
6. Miles F, Djellouli F, Bensiradj N, Dahmani A. Pharmaceutical cocrystal consisting of ascorbic acid with p-aminobenzoic acid and paracetamol. Physical Sciences Reviews. 2022; 137-50. https://doi.org/10.1515/psr-2021-0199
7. Devi V, Kaur B, Gupta M, Singh G. Comparative studies of molecular modification approach to enhance the solubility of gefitinib. 2022; 21(8): 1189-232.
8. Gaddam M, Ravouru N. A Crystal Engineering design to enhance the Solubility, Dissolution, Stability and Micrometric properties of Omeprazole via Co-crystallization Techniques. Research Journal of Pharmacy and Technology. 2021; 14(1): 356-62. DOI:10.5958/0974-360X.2021.00065.2
9. Chandur VK, George P, Shabaraya AR. Solubility enhancement of risperidone by cocrystallisation. EJBPS. 2022; 9(12).
10. Xia M, Jiang Y, Cheng Y, Dai W, et al Rucaparib cocrystal: Improved solubility and bioavailability over camsylate. International Journal of Pharmaceutics. 2023; 631: 122461. https://doi.org/10.1016/j.ijpharm.2022.122461
11. Kemisetti D, Amin R, Alam F, Gacem A, et al. Novel Benzothiazole Derivatives Synthesis and its Analysis as Diuretic Agents. Evidence-Based Complementary and Alternative Medicine. 2023. https://doi.org/10.1155/2023/5460563
12. Pantwalawalkar J, More H, Bhange D, Patil U, Jadhav N. Novel curcumin ascorbic acid cocrystal for improved solubility. J Drug Deliv Sci Technol. 2021; 61: 1022-33. https://doi.org/10.1016/j.jddst.2020.102233
13. Saini M, Das R, Mehta DK. Design, Synthesis, and Pharmacological Evaluation of Substituted Oxadiazole-Pyridazin-3-One Derivatives as Antioxidant and Antimicrobial Agents. Anti-Infective Agents. 2022; 20(4): 36-45. https://doi.org/10.2174/2211352520666220317142519
14. Chopade DR, Patil PM, Suryawanshi MB. In silico Molecular docking of Herbal plant extract for Antioxidant activity. Journal For Basic Sciences. 2022; 22(12): 256-61.
15. Connors KA, Higuchi T. Phase solubility techniques. Adv. Anal. Chem. Instrum. 1965; 4: 117-212.
16. Sahoo AC, Kanungo SK, Dinda SC, Dash S, et al. Formulation Development of Immediate Release Solid Dispersion Tablets of Lovastatin with Enhanced Dissolution. Research Journal of Pharmacy and Technology. 2019; 12(10): 4963-72. DOI: 10.5958/0974-360X.2019.00861.8
17. Dash S. Studies of thermal, spectral and antibacterial activities of some inclusion complexes of 4-Thiazolidinone derivatives with β-Cyclodextrin. 2022; 15(1); 65-70. DOI: 10.52711/0974-4150.2022.00010
18. Srinivasan S, Elhassan Go, Janakiraman Ak, Kayarohanam S, et al Preparation And Characterization Of Etoricoxib Ternary Complex For The Enhancement Of Solubility. Journal of Pharmaceutical Negative Results. 2023; 1703-12. DOI: https://doi.org/10.47750/pnr.2023.14.02.216
19. Ge X, Huang Z, Tian J, Xu R, Wu X, Tian S. S-(+)-carvone/HPβCD inclusion complex: Preparation, characterization and its application as a new sprout suppressant during potato storage. Food Chemistry Advances. 2022; 1: 100100. https://doi.org/10.1016/j.focha.2022.100100
20. Winantari AN, Setyawan D, Soewandhi SN. Solid state characterization of acyclovir-nicotinamide binary systems using solvent evaporation technique. Asian Journal of Pharmacy and Technology. 2017; 7(1): 33-6. DOI: 10.5958/2231-5713.2017.00006.X
21. Mishra SP. Introducing of thermodynamic Van’t Hoff equation in process of dissociation of benzoic acid at ordinary temperature range. Chemical Science International Journal. 2022; 31(1): 8-14.
22. Inam S, Irfan M, Lali NU, Khalid Syed Het al.. Development and characterization of eudragit® EPO-based solid dispersion of rosuvastatin calcium to foresee the impact on solubility, dissolution and antihyperlipidemic activity. Pharmaceuticals. 2022; 15(4): 492. https://doi.org/10.3390/ph15040492
23. Ibrahim AH, Ibrahim HM, Elbahwy IA, Afouna MI, et al. Lyophilized tablets of felodipine-loaded polymeric nanocapsules to enhance aqueous solubility: Formulation and optimization. Journal of Drug Delivery Science and Technology. 2022; 70: 103172. https://doi.org/10.1016/j.jddst.2022.103172
24. Rao MR, Sonawane AS, Sapate SA, et al. Molecular modeling and in vitro studies to assess solubility enhancement of nevirapine by solid dispersion technique. Journal of Molecular Structure. 2023;1273:134373. https://doi.org/10.1016/j.molstruc.2022.134373
25. Latha AV, Ravikiran TN, Kumar JN. Formulation, Optimization and Evaluation of Glibenclamide Transdermal Patches by using chitosan Polymer. Asian Journal of Pharmacy and Technology. 2019; 9(1): 1-7. DOI: 10.5958/2231-5713.2019.00001.1
26. Zuccari G, Russo E, Villa C, Zorzoli A, et al. Preparation and Characterization of Amorphous Solid Dispersions for the Solubilization of Fenretinide. Pharmaceuticals. 2023; 16(3): 388. https://doi.org/10.3390/ph16030388
27. Kumar D, Talegaonkar S, Bedi S, Dubey K. Design, development and evaluation of self-microemulsifying drug delivery system of pazopanib for enhanced dissolution rate and cytotoxic potential. Journal of Drug Delivery Science and Technology. 2023; 104181.https://doi.org/10.1016/j.jddst.2023.104181
28. Priyadarshini P, Karwa P, Syed A, Asha AN. Formulation and Evaluation of Nanoemulgels for the Topical Drug Delivery of Posaconazole. Journal of Drug Delivery and Therapeutics. 2023; 13(1): 3-43. https://doi.org/10.22270/jddt.v13i1.5896
29. Wagh PK, Ahirrao SP, Kshirsagar SJ. Novel mucoadhesive gastro retentive drug delivery system of ranitidine hydrochloride. Asian Journal of Pharmaceutical Research. 2019; 9(2): 80-6.
30. Sultan MH, Moni SS, Madkhali OA, Bakkari MA,et al. Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer. Scientific Reports. 2022; 12(1): 468. https://doi.org/10.1038/s41598-021-04427-w
31. Zidan MF, Afouna MI, Ismael HR, Ibrahim MF. Enhancement of Glimepiride Bioavailability by Co-Crystallization Technique. IJRASET. 2023;11(II): 561-68.
32. Mandake GR, Shinde SS, Patil OA, Nitalikar MM. Dissolution enhancement of Telmisartan by spray drying technique. Asian Journal of Pharmacy and Technology. 2018; 8(4): 264-9. DOI: 10.5958/2231-5713.2018.00041.7
33. Yadav D, Savjani J, Savjani K, Kumar A, Patel S. Pharmaceutical Co-crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability. AAPS Pharm Sci Tech. 2022; 24(1): 7. https://doi.org/10.1208/s12249-022-02467-7
34. Gowda BJ, Nechipadappu SK, Shankar SJ, Chavali M, et al. Pharmaceutical cocrystals of efavirenz: Towards the improvement of solubility, dissolution rate and stability. Materials Today: Proceedings. 2022; 51: 394-402. https://doi.org/10.1016/j.matpr.2021.05.535
35. Dutta A, Mondal S, Singh PK, Ray B. Single crystal investigation, Hirshfeld surface and interaction energy framework analyses of structure-directing interactions within two isomorphous Schiff's base multicomponent salts. Journal of Molecular Structure. 2022 ; 1264: 133224. https://doi.org/10.1016/j.molstruc.2022.133224
36. Rathore SK, Pathak BK. Formulation and evaluation of aceclofenac-loaded nanoparticles by solvent evaporation method. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020; 12(4): 237-44. DOI: 10.5958/0975-4377.2020.00039.7
37. Gowda BJ, Nechipadappu SK, Shankar SJ, Chavali M, et al. Pharmaceutical cocrystals of efavirenz: Towards the improvement of solubility, dissolution rate and stability. Materials Today: Proceedings. 2022; 51: 394-402. https://doi.org/10.1016/j.matpr.2021.05.535
38. Bingidoddi P, Marabathuni VJ, Narapusetty N. Formulation development and invitro evaluation of efavirenz cyclodexprin complexes im-mediate release tablets. International Journal of Pharmacognosy and Chemistry. 2022; 10-5. https://doi.org/10.46796/ijpc.v3i1.263
39. Wadaskar P, Kharkar P, Ispade P. Preparation and Evaluation of Yohimbine Hydrochloride Agglomerates by Crystallo Co-Agglomeration Technique. 2022; 14(2); 105-10. DOI: 10.52711/0975-4377.2022.00016
40. Jyothi VG, Bulusu R, Rao BV, Pranothi M, et al. Stability characterization for pharmaceutical liposome product development with focus on regulatory considerations: An update. International Journal of Pharmaceutics. 2022; 122022. https://doi.org/10.1016/j.ijpharm.2022.122022
41. Sahoo CK, Rao SR, Sudhakar M, Ramana DV, Panda KC. Formulation and Evaluation of Controlled Porosity Osmotic Pump Tablets for Oral Delivery of Stavudine. Research Journal of Pharmaceutical Dosage Forms and Technology. 2018;10(3):179-87. DOI: 10.5958/0975-4377.2018.00028.9
42. Manasa M, Ravali A, Bargavi B, Mounica B, Prasanna VL. Comparative Stability Study of Vitamin C present in Fresh Lemon Juice and Marketed Juice by Analytical Methods. Research Journal of Pharmacy and Technology. 2019; 12(10): 4724-8. DOI: 10.5958/0974-360X.2019.00814.X
43. Usta DY, Incecayir T. Modeling of in vitro dissolution profiles of carvedilol immediate-release tablets in different dissolution media. AAPS Pharm Sci Tech. 2022; 23(6): 201. https://doi.org/10.1208/s12249-022-02355-0
44. Tessema FB, Gonfa YH, Asfaw TB, Tadesse MG, Bachheti RK. Antioxidant activity of flavonoids and phenolic acids from Dodonaea angustifolia flower: HPLC profile and PASS prediction. Journal of Chemistry. 2023; 2023. https://doi.org/10.1155/2023/8315711