Volume : 13, Issue : 07, July – 2026

Title:

BOX–BEHNKEN OPTIMIZED Β-CYCLODEXTRIN NANOSPONGES OF LAPATINIB DITOSYLATE: SOLID-STATE CHARACTERIZATION, IN-VITRO RELEASE, AND ENHANCED ORAL BIOAVAILABILITY IN RATS

Authors :

M. Bhargavi*, Dr. Ram Prasad

Abstract :

Lapatinib Ditosylate carries a familiar liability for a modern kinase inhibitor: pH-dependent aqueous solubility paired with dual P-glycoprotein/BCRP efflux, a combination that together caps and destabilizes what fraction of an oral dose ever reaches the systemic circulation (Polli et al., 2008; FDA, 2010). To address this, diphenyl-carbonate-crosslinked β-cyclodextrin (β-CD) Nanosponges were designed and optimized as an oral carrier using a three-factor, three-level Box–Behnken design (BBD), with β-CD: diphenyl carbonate (DPC) molar ratio, stirring speed, and drug: carrier ratio as independent variables mapped against particle size, entrapment efficiency (EE), and 24-hour cumulative release. Phase-solubility analysis returned an A_L-type profile, an apparent stability constant of 1245 M⁻¹, and a 21.7-fold solubility gain at 16 mM β-CD. The optimized batch — F11, at a β-CD:DPC ratio near 1:5.2, drug: carrier 1:3, and 1100 rpm — produced particles of 212.8 ± 4.6 nm with a polydispersity index of 0.231 ± 0.018, a zeta potential of −24.3 ± 1.3 mV, and 80.6 ± 1.4% entrapment efficiency; predicted and observed values agreed within 1.5% across every response. FTIR, DSC, and PXRD converged on a single structural story: carbonate-ester crosslinking had occurred, and the entrapped drug had lost essentially all long-range crystalline order. F11 released 87.2 ± 1.6% of its lapatinib payload within 24 hours at pH 1.2 against 21.6% for the free drug, tracking Korsmeyer–Peppas anomalous-transport kinetics (R² = 0.9893, n = 0.493), and stayed within regulatory drift limits across three months of accelerated storage. In Sprague-Dawley rats, F11 lifted the area under the plasma concentration–time curve 3.91-fold and raised absolute oral bioavailability from 13.6% to 52.1% relative to free lapatinib, with a delayed time-to-peak concentration that fits a sustained, cavity-mediated release pattern. Taken together, the data position carbonate-crosslinked β-CD Nanosponges as a workable, scalable solid oral platform for lapatinib — and, plausibly, for structurally related tyrosine-kinase inhibitors facing the same dissolution-and-efflux bottleneck.
Keywords: Lapatinib, Nanosponges, Box-Behnken design, Pharmacokinetics.

Cite This Article:

Please cite this article in press M. Bhargavi et al., Box–Behnken Optimized Β-Cyclodextrin Nanosponges Of Lapatinib Ditosylate: Solid-State Characterization, In-Vitro Release, And Enhanced Oral Bioavailability In Rats.,, Indo Am. J. P. Sci, 2026; 13(07).

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