Majority of conventional oral delivery fails to maintain therapeutic concentration of drugs at site of action due to fast gastric-emptying time. Therefore, to overcome these inherent limitations and to improve pharmacokinetic parameters, a porous calcium silicate, fluorite (Florite RE®: FLR) and low methoxy (LM) pectin-based floating-pulsatile drug delivery system was developed for engineered specific drug release of nifedipine (NFD). FLR was investigated as multifaceted acting agent to act as solublizer and to impart pulsatile release. FLR-based NFD-loaded floating-pulsatile pectin beads were prepared using ionotropic gelation technique and optimized via 32 factorial design. Concentration of FLR-adsorbed NFD (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">${X}_{1}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>X</mi> <mn>1</mn> </msub> </math></EquationSource> </InlineEquation>) and LM pectin (<InlineEquation ID="IEq2"> <EquationSource Format="TEX">${X}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>X</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation>) was used as independent variables, while lag time (<InlineEquation ID="IEq3"> <EquationSource Format="TEX">${Y}_{1}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>1</mn> </msub> </math></EquationSource> </InlineEquation>) and floating time (<InlineEquation ID="IEq4"> <EquationSource Format="TEX">${Y}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation>) were tested as response variables. Prepared beads were evaluated for entrapment efficiency, mechanical strength, floating time, in vitro dissolution, and in vivo pharmacokinetic studies. Optimized formulation (F4) showed lag time of 6.00 ± 0.21 h and released ~ 100% of drug from beads within 1.5 h after a lag time. Furthermore, <InlineEquation ID="IEq5"> <EquationSource Format="TEX">${X}_{1}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>X</mi> <mn>1</mn> </msub> </math></EquationSource> </InlineEquation> showed significant positive effect on <InlineEquation ID="IEq6"> <EquationSource Format="TEX">${Y}_{1}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>1</mn> </msub> </math></EquationSource> </InlineEquation> and <InlineEquation ID="IEq7"> <EquationSource Format="TEX">${Y}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation>, whereas <InlineEquation ID="IEq8"> <EquationSource Format="TEX">${X}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>X</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation> exhibited significant positive and negative effect on <InlineEquation ID="IEq9"> <EquationSource Format="TEX">${Y}_{1}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>1</mn> </msub> </math></EquationSource> </InlineEquation> and <InlineEquation ID="IEq10"> <EquationSource Format="TEX">${Y}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>Y</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation> respectively. Additionally, FLR-NFD-based beads demonstrated improvement in bioavailability of drug tested by 1.90-folds, compared to its native form–loaded beads. This two-stage approach could emerge as a promising approach to get relief from cardiac disorders that follows biological clock. Graphical abstract

Quality by design approach for nifedipine-adsorbed fluorite-loaded calcium-low methoxy pectin beads to impart chronotherapy: in vitro and in vivo assessment

期刊论文
发表日期：

2025年6月28日

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Rajesh S. Jagtap,
Shrinivas K. Mohite,
Sneha R. Jagtap,
Sameer J. Nadaf,
Sachin S. Mali,
Poournima S. Sankpal,
Sudarshan Singh

摘要

Majority of conventional oral delivery fails to maintain therapeutic concentration of drugs at site of action due to fast gastric-emptying time. Therefore, to overcome these inherent limitations and to improve pharmacokinetic parameters, a porous calcium silicate, fluorite (Florite RE®: FLR) and low methoxy (LM) pectin-based floating-pulsatile drug delivery system was developed for engineered specific drug release of nifedipine (NFD). FLR was investigated as multifaceted acting agent to act as solublizer and to impart pulsatile release. FLR-based NFD-loaded floating-pulsatile pectin beads were prepared using ionotropic gelation technique and optimized via 3² factorial design. Concentration of FLR-adsorbed NFD ( ${X}_{1}$ $X_{1}$ ) and LM pectin ( ${X}_{2}$ $X_{2}$ ) was used as independent variables, while lag time ( ${Y}_{1}$ $Y_{1}$ ) and floating time ( ${Y}_{2}$ $Y_{2}$ ) were tested as response variables. Prepared beads were evaluated for entrapment efficiency, mechanical strength, floating time, in vitro dissolution, and in vivo pharmacokinetic studies. Optimized formulation (F4) showed lag time of 6.00 ± 0.21 h and released ~ 100% of drug from beads within 1.5 h after a lag time. Furthermore, ${X}_{1}$ $X_{1}$ showed significant positive effect on ${Y}_{1}$ $Y_{1}$ and ${Y}_{2}$ $Y_{2}$ , whereas ${X}_{2}$ $X_{2}$ exhibited significant positive and negative effect on ${Y}_{1}$ $Y_{1}$ and ${Y}_{2}$ $Y_{2}$ respectively. Additionally, FLR-NFD-based beads demonstrated improvement in bioavailability of drug tested by 1.90-folds, compared to its native form–loaded beads. This two-stage approach could emerge as a promising approach to get relief from cardiac disorders that follows biological clock.

Graphical abstract