FORMULATION AND EVALUATION OF EFFERVESCENT GRANULES CONTAINING ANTIRETROVIRAL AGENT SOLID DISPERSIONS FOR CHILDREN AND ELDERS: SOLUBILITY ENHANCEMENT, DISSOLUTION RATE AND INTEGRATION INHIBITION EFFECT

SUNITHA SAMPATHI; LAKSHMI DEVI GOTTEMUKKULA; B. AISHWARYA; M. JYOTHIRADITYA; B. MANIKANTH

doi:10.22159/ijap.2025v17i6.55697

Authors

SUNITHA SAMPATHI Department of Pharmacy, Vishwakarma University, Pune, Maharashtra, India
LAKSHMI DEVI GOTTEMUKKULA Joginpally B. R. Pharmacy College, Moinabad, R. R. District, Hyderabad, Telangana-500075, India https://orcid.org/0000-0002-8300-0465
B. AISHWARYA Joginpally B. R. Pharmacy College, Moinabad, R. R. District, Hyderabad, Telangana-500075, India
M. JYOTHIRADITYA Joginpally B. R. Pharmacy College, Moinabad, R. R. District, Hyderabad, Telangana-500075, India
B. MANIKANTH Joginpally B. R. Pharmacy College, Moinabad, R. R. District, Hyderabad, Telangana-500075, India

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55697

Keywords:

Captisol®, Effervescent granules, Fusion method, Solid dispersions, solubility enhancement

Abstract

Objective: Dolutegravir inhibits viral replication by blocking the integrase strands. To treat human immunodeficiency virus (HIV), it is one of the medications used in children and the elderly. It is difficult to get a high oral bioavailability of dolutegravir because of these population issues with swallowing and ineffective absorption, as well as the drug's intrinsic poor solubility and instability in stomach acid. To address these problems, we created and described effervescent granules containing a solid dolutegravir dispersion.

Methods: The melt granulation process was used with various categories and quantities of polymers to develop solid dispersion-based effervescent granules. The solid dispersions were prepared using four different methods: Physical Mixing, Co-grinding, Kneading and fusion methods. Drug-to-carrier ratios of 1:1, 1:2, 1:3, and 1:4 were investigated. To develop solid dispersions, three generations of polymers are selected [crystalline carrier (mannitol), Amorphous carriers [polyethene glycol (PEG 4000), polyvinyl pyrrolidone (PVP K90), hydroxypropyl methylcellulose (HPMC E5LV), sulfobutylether-Captisol (captisol)], poloxamer 188 and poloxamer 407].

Results: The DTG and the chosen polymer are compatible, according to FTIR studies; DSC and XRD results reveal crystalline changes of DTG; surface morphology reveals that pure DTG has a crystalline prismatic shape. Second, a total of 12 formulations of the effervescent granules containing the solid dispersion were developed using various excipients such as sweeteners, gas generators, pH modulators, and glidants/lubricants. The results show that all 12 formulations had a good release profile within 5 min. F3 shows the highest drug content (99.5±0.11), the highest percentage of drug release 99.5% within 5 min and the effervescent cessation time 19.5±2.12 sec. The good release profile of F3 may be attributed to the combination of cetyl alcohol and sodium starch glycolate.

Conclusion: Additional in vivo and clinical research may be conducted on the final effervescent granule product to develop it into a dolutegravir delivery system with high bioavailability for older people and children.

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