Author(s):
Neha Srivastava, Maninderpreet Kaur, Seema Thakur, Amardeep Kaur
Email(s):
nehasrvstva@gmail.com
DOI:
10.52711/0974-360X.2025.00822 
Address:
Neha Srivastava1, Maninderpreet Kaur2, Seema Thakur3, Amardeep Kaur4
1School of Pharmaceutical Sciences, RIMT University, Mandi Gobindgarh, Punjab, India.
2Swami Vivekanand Institute of Pharmacy, Zirakpur-Patiala Highway, Ram Nagar, Banur, Punjab.
3PCTE group of institutes, Faculty of Pharmaceutical Sciences, Ludhiana, Punjab, India.
4PCTE group of institutes, Faculty of Pharmaceutical Sciences, Ludhiana, Punjab, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 12,
Year - 2025
ABSTRACT:
Fourth-generation solid dispersion (FG-SD) is the one-step strategy to improve solubility and control drug liberation from the solid dispersion matrix. FG-SD can be developed using a combination of different polymers. In the present work, FG-SD of drug cefixime (CFX) was prepared using a combination of hydrophobic polymers such as cetyl alcohol (CA) and stearic acid (SA), and hydrophilic polymer such as hydroxyl propyl methyl cellulose (HPMC) K4M. CFX belongs to the BCS class IV, indicating poor solubility and poor permeability. Thus, formulation of FG-SD of CFX (FG-SD-CFX) gives a one-step goal that will help to improve the drug CFX solubility and help to manage the drug release in a sustained manner. 12 different formulations were developed using various combinations of HPMC, CA, and SA. The prepared formulation FG-SD-CFX was studied using solubility tests, drug content, and in vitro dissolution studies. The optimized FG-SD-CFX was characterized using Fourier Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffraction (PXRD), and differential scanning calorimetry (DSC). All the formulations developed showed a considerable enhancement in the aqueous solubility of the drug than the plain drugs and exhibited uniform drug content. In vitro studies data reveal that CFX-CA-4 formulation exhibits 93.23% drug release in 24 h. The release kinetics was studied for all the FTIR studies, confirmed that no interactions were observed between the drug and polymers. The PXRD results confirm the formation of an amorphous structure. DSC studies further confirm the conversion of crystalline CFX to an amorphous form, which is supported by the change in ?H value. Thus, from the study, it can be concluded that the FG-SD is the novel single-step approach that can improve drug release and modify the release of drugs in a sustained manner for the BCS class IV drug CFX. DSC studies confirm the formation of a drug and polymer complex. Thus, from the studies, it can be concluded that FG-SD is an efficient method that can serve a dual purpose of improving the solubility of the drug and sustaining the release in a single step for the drug cefixime.
Cite this article:
Neha Srivastava, Maninderpreet Kaur, Seema Thakur, Amardeep Kaur. Fourth-generation Solid Dispersion of Poorly Water-soluble Cefixime Trihydrate: Development and Optimization. Research Journal Pharmacy and Technology. 2025;18(12):5693-1. doi: 10.52711/0974-360X.2025.00822
Cite(Electronic):
Neha Srivastava, Maninderpreet Kaur, Seema Thakur, Amardeep Kaur. Fourth-generation Solid Dispersion of Poorly Water-soluble Cefixime Trihydrate: Development and Optimization. Research Journal Pharmacy and Technology. 2025;18(12):5693-1. doi: 10.52711/0974-360X.2025.00822 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-12-12
REFERENCES:
1. Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in oral drug delivery. Frontiers in Pharmacology. 2021; Feb 19; 12: 618411: 1-21 . https://doi.org/10.3389/fphar.2021.618411
2. Zhang Y, Jiang R, Lei L, Yang Y, Hu T. Drug delivery systems for oral disease applications. Journal of Applied Oral Science. 2022; Mar 9; 30: e20210349, 1-12. http://dx.doi.org/10.1590/1678-7757-2021-0349
3. Shinkar DM, Patil AN, Saudagar RB. Solubility and dissolution enhancement of sulfasalazine by the solid dispersion technique. Research Journal of Pharmacy and Technology. 2018; 11(4): 1277-82.
4. Laffleur F, Keckeis V. Advances in drug delivery systems: Work in progress still needed? International journal of pharmaceutics. 2020; Nov 30; 590: 119912: 1-15. 10.1016/j.ijpharm.2020.119912
5. Viswanathan P, Muralidaran Y, Raghavan G. Challenges in oral drug delivery: a nano-based strategy to overcome. In Nanostructures for oral Medicine 2017; Jan 1: (pp. 173-201). Elsevier.
6. Kaur G, Arora M, Kumar MR. Oral drug delivery technologies—a decade of developments. Journal of Pharmacology and Experimental Therapeutics. 2019; Sep 1; 370(3): 529-43. 10.1124/jpet.118.255828
7. Tabanelli R, Brogi S, Calderone V. Improving curcumin bioavailability: Current strategies and future perspectives. Pharmaceutics. 2021; Oct 17; 13(10): 1715. 10.3390/pharmaceutics13101715
8. Bolla G, Sarma B, Nangia AK. Crystal engineering of pharmaceutical cocrystals in the discovery and development of improved drugs. Chemical Reviews. 2022; Jun 1; 122(13): 11514-603. 10.1021/acs.chemrev.1c00987
9. Ha ES, Lee SK, Choi DH, Jeong SH, Hwang SJ, Kim MS. Application of diethylene glycol monoethyl ether in solubilization of poorly water-soluble drugs. Journal of Pharmaceutical Investigation. 2020; May; 50: 231-50. 10.1007/s40005-019-00454-y
10. Saal W, Ross A, Wyttenbach N, Alsenz J, Kuentz M. Unexpected solubility enhancement of drug bases in the presence of a dimethylaminoethyl methacrylate copolymer. Molecular pharmaceutics. 2018; Jan 2; 15(1): 186-92. 10.1021/acs.molpharmaceut.7b00804
11. Pires PC, Rodrigues M, Alves G, Santos AO. Strategies to improve drug strength in nasal preparations for brain delivery of low aqueous solubility drugs. Pharmaceutics. 2022; Mar 8; 14(3): 588. https://doi.org/10.3390/pharmaceutics14030588
12. Moriwaki C, Costa GD, Ferracini CN, De Moraes FF, Zanin GM, Pineda EA, Matioli G. Enhancement of solubility of albendazole by complexation with β-cyclodextrin. Brazilian Journal of Chemical Engineering. 2008; 25: 255-67. https://doi.org/10.1590/S0104-66322008000200005
13. Loh GO, Tan YT, Peh KK. Enhancement of norfloxacin solubility via inclusion complexation with β-cyclodextrin and its derivative hydroxypropyl-β-cyclodextrin. Asian Journal of Pharmaceutical Sciences. 2016; Aug 1; 11(4): 536-46. 10.1016/j.ajps.2016.02.009
14. Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS Pharmscitech. 2006; Sep; 7(3): 68. 10.1208/pt070368
15. Hammond RB, Pencheva K, Roberts KJ, Auffret T. Quantifying solubility enhancement due to particle size reduction and crystal habit modification: case study of acetyl salicylic acid. Journal of Pharmaceutical Sciences. 2007; Aug 1; 96(8): 1967-73. 10.1002/jps.20869
16. Sai KK. Formulation and Evaluation of Solid Dispersion of Phenytoin by Solvent Evaporation Technique. Asian Journal of Pharmaceutical Research. 2024; Sep 20; 14(3): 199-205.
17. Galam AG, Shahi SR, Deore S, Fatema QI. Solid Dispersion: Recapitulation. Asian Journal of Pharmacy and Technology. 2020; 10(2): 107-17.
18. Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Advanced pharmaceutical bulletin. 2020; Jul; 10(3): 359-369. 10.34172/apb.2020.044
19. Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. International Journal of Pharmaceutics. 2020; Aug 30; 586: 119560: 1-42. 10.1016/j.ijpharm.2020.119560.
20. Mahore JG, Deshkar SS, Kumare PP. Solid dispersion technique for solubility improvement of ketoconazole for vaginal delivery. Research Journal of Pharmacy and Technology. 2019; 12(4): 1649-54.
21. Salman ZD. Optimization and evaluation of orodispersible solid dispersion tablet of ketotifen fumarate. Research Journal of Pharmacy and Technology. 2021; 14(7): 3610-6.
22. Jadav NB, Paradkar A. Solid dispersions: technologies used and future outlook. In Nanopharmaceuticals 2020; Jan 1 (pp. 91-120). Elsevier. https://doi.org/10.1016/B978-0-12-817778-5.00005-1.
23. Aher SS, Songire PR, Saudagar RB. Formulation and evaluation of controlled release matrix tablet of albuterol sulphate. Asian Journal of Research in Pharmaceutical Science. 2016; 6(4): 223-9.
24. Reddy YK, Bharani V. Formulation and Evaluation of Oral Controlled Release Tablets of Milnacipran Hydrochloride. Asian Journal of Research in Pharmaceutical Science. 2020; 10(2): 95-9.
25. Reddy YK, Giri K. Preparation and In vitro Characterisation Venlafaxine HCl Controlled Release Tablets. Asian Journal of Pharmacy and Technology. 2020; 10(2): 81-4.
26. Malkawi R, Malkawi WI, Al-Mahmoud Y, Tawalbeh J. Current trends on solid dispersions: past, present, and future. Advances in Pharmacological and Pharmaceutical Sciences. 2022; 2022(1): 5916013. 10.1155/2022/5916013
27. Alshehri, S., Imam, S.S., Hussain, A., Altamimi, M.A., Alruwaili, N.K., Alotaibi, F., Alanazi, A. and Shakeel, F., 2020. RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents. Drug delivery, 27(1), pp.1625-1643. 10.1080/10717544.2020.1846638
28. Patel K, Shah S, Patel J. Solid dispersion technology as a formulation strategy for the fabrication of modified release dosage forms: A comprehensive review. DARU Journal of Pharmaceutical Sciences. 2022; Jun; 30(1): 165-89. 10.1007/s40199-022-00440-0
29. Bhaduka G, Rajawat JS. Formulation development and solubility enhancement of voriconazole by solid dispersion technique. Research Journal of Pharmacy and Technology. 2020; 13(10): 4557-64.
30. Saker R, Ibrahim W, Haroun M. Preparation and evaluation of nifedipine solid dispersions. Research Journal of Pharmacy and Technology. 2020; 13(9): 4148-52.
31. Schver GC, Nadvorny D, Lee PI. Evolution of supersaturation from amorphous solid dispersions in water-insoluble polymer carriers: Effects of swelling capacity and interplay between partition and diffusion. International Journal of Pharmaceutics. 2020; May 15; 581: 119292. http://dx.doi.org/10.1016/j.ijpharm.2020.119292
32. Cefixime, Cefixime | C16H15N5O7S2 | CID 5362065 - PubChem (nih.gov), 27 July 2024.
33. Panthi VK, Fairfull-Smith KE, Islam N. Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives. Pharmaceutics. 2024; May 11; 16(5): 648. https://doi.org/10.3390/pharmaceutics16050648
34. Muteeb G, Rehman MT, Shahwan M, Aatif M. Origin of antibiotics and antibiotic resistance, and their impacts on drug development: A narrative review. Pharmaceuticals. 2023; Nov 15; 16(11): 1615. https://doi.org/10.3390/ph16111615
35. Mahore JG, Deshkar SS, Kumare PP. Solid dispersion technique for solubility improvement of ketoconazole for vaginal delivery. Research Journal of Pharmacy and Technology. 2019; 12(4): 1649-54.
36. Sarkar S, Srivastava V, Samajhdar SS, Pattanayak C, Tripathi S. Rational use of antibiotics: an area of concern. Journal of Young Pharmacists. 2022; Apr; 14(2): 165. 10.5530/jyp.2022.14.31
37. Kim, D. S., Choi, H.-G., and Jin, S. G. (2018). Influence of Hydroxypropylmethylcellulose and Sodium Lauryl Sulfate on the Solubility and Dissolution of Sirolimus in Solvent-evaporated Solid Dispersions. Bulletin of the Korean Chemical Society, 39(6), 778–783. https://doi.org/10.1002/bkcs.11470
38. Mahmood A, Khan L, Ijaz M, Nazir I, Naseem M, Tahir MA, Aamir MN, Rehman MU, Asim MH. Enhanced intestinal permeability of cefixime by self-emulsifying drug delivery system: in-vitro and ex-vivo characterization. Molecules. 2023; Mar 21; 28(6): 2827. https://doi.org/10.3390/molecules28062827
39. Yu S, Xue FM, Cheng Y. Solubility of Cefixime Disodium in Seven Pure Solvents. Russian Journal of Physical Chemistry A. 2020; Jun; 94: 1130-5. 10.1134/S0036024420060333
40. Pathan D, Memon S, Siddique A. Enhancement of in-vitro dissolution efficiency of cefixime trihydrate using natural polymer by solid dispersion technique. Journal of Current Pharma Research. 2020; Jul 1; 10(4): 3907-18.
41. Paarakh PM, Jose PA, Setty CM, Peter GV. Christoper3 Release Kinetics – Concepts And Applications, International Journal Of Pharmaceutical Research and Technology. 2018; 10 -2018: 12-20.
42. Shafiei F, Ghavami-Lahiji M, Jafarzadeh Kashi TS, Najafi F. Drug release kinetics and biological properties of a novel local drug carrier system. Dent Res J (Isfahan). 2021; Nov 22; 18: 94. doi: 10.4103/1735-3327.330875. PMID: 35003559; PMCID: PMC8672127. 10.4103/1735-3327.330875
43. Balogun-Agbaje OA, Usman F, Ladele F, Oyegunju A, Sowunmi A, Babalola CO, Uwaezuoke OJ, Bamiro O, Bakre LG. Enhancement of cefixime solubility using a ternary solid dispersion system containing starch isolated from maize genotype. West African Journal of Pharmacy. 2024; Apr 15; 35(1): 32-44. https://doi.org/10.60787/wapcp-v35i1-334
44. Chaturvedi PR, Soni PK, Paswan SK. Designing and development of gastroretentive mucoadhesive microspheres of cefixime trihydrate using spray dryer. Int. J. App. Pharm.. 2023; Mar 7; 15: 185-93. https://dx.doi.org/10.22159/ijap.2023v15i2.45399
45. Kong R, Xu L, Zhu L, Sun Y. Preparation, characterization and evaluation of cefixime ternary inclusion complexes formated by mechanochemical strategy. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2024; Feb; 104(1): 51-71. https://ssrn.com/abstract=4681358 or http://dx.doi.org/10.2139/ssrn.4681358
46. Li N, Taylor LS. Tailoring supersaturation from amorphous solid dispersions. Journal of Controlled Release. 2018; Jun 10; 279: 114-25. 10.1016/j.jconrel.2018.04.014
47. França MT, Pereira RN, Riekes MK, Pinto JM, Stulzer HK. Investigation of novel supersaturating drug delivery systems of chlorthalidone: The use of polymer-surfactant complex as an effective carrier in solid dispersions. European Journal of Pharmaceutical Sciences. 2018; Jan 1; 111: 142-52. 10.1016/j.ejps.2017.09.043
48. Mahdi Alsammarraie HJ, Alabasi MA, Karim Khan NA. Impact of hydroxy propyl methyl cellulose on drug release profile and drug release kinetics of Moringa extract formulated as granules. International Journal of Pharmaceutical Research (09752366). 2020; Jul 2.
49. Vrettos NN, Roberts CJ, Zhu Z. Gastroretentive technologies in tandem with controlled-release strategies: A potent answer to oral drug bioavailability and patient compliance implications. Pharmaceutics. 2021; Sep 30; 13(10): 1591. 10.3390/pharmaceutics13101591
50. Kalyani Sakure, Leena Kumari, Hemant Badwaik, Development and evaluation of solid dispersion based rapid disintegrating tablets of poorly water-soluble anti-diabetic drug, Journal of Drug Delivery Science and Technology, Volume 60, 2020, 101942; 1773-2247.