Pediatric powder for oral suspension containing antiviral agent and method for the preparation thereof
Inventors
Karavas, Evangelos • KOUTRIS, EFTHYMIOS • SAMARA, VASILIKI • Koutri, Ioanna • Kalaskani, Anastasia • Kalantzi, Lida • KAKOURIS, ANDREAS • Diakidou, Amalia • GOTZAMANIS, GEORGE • GEORGOUSIS, ZAHARIAS • FOUSTERIS, MANOLIS
Assignees
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Publication Number
US-12458645-B2
Publication Date
2025-11-04
Expiration Date
Abstract
A powder including Valaciclovir or pharmaceutical acceptable salt or derivative thereof and an ion exchange resin. The Valaciclovir is in complex with the ion exchange resin forming Drug-Resin complex (DRC) particles, and each DRC particle comprises hydrogen bonds between the ion exchange resin and a cationic center of Valaciclovir. The ratio of Valaciclovir to the ion exchange resin in the DRC particle is 1:0.5. The powder further includes a suspending agent and a pH agent, and the suspending agent forms a film around each DRC particle and the film decreases interparticle attraction. The powder is configured to be reconstituted with an aqueous diluent as suspension for oral administration.
Core Innovation
The invention relates to a pediatric oral-suspension powder containing Valaciclovir, or a pharmaceutical acceptable salt or derivative thereof, complexed with an ion exchange resin to form drug-resin complex particles. The DRC particles include hydrogen bonds between the ion exchange resin and a cationic center of Valaciclovir, and the ratio of Valaciclovir to the ion exchange resin in the DRC particle is 1:0.5. The powder is configured to be reconstituted with an aqueous diluent to form a homogeneous suspension for oral administration.
To address interparticle attraction and improve resuspendability and taste masking upon reconstitution, the powder further comprises a suspending agent that is xanthan gum. The suspending agent forms a film around each DRC particle, and the film decreases interparticle attraction. The powder optionally comprises a pH agent.
The disclosed formulation has a dissolution profile in which more than 95% of Valaciclovir is released from complexation at 10 minutes when suspended in 900 ml HCl 0.1N. The document also describes formation of DRC particles by complexing Valaciclovir with an ion exchange resin, milling to a particle size less than 250 μm, and forming a powder with an internal phase and an external phase including xanthan gum and optionally a pH agent.
Claims Coverage
The independent claims cover three main inventive feature blocks: Valaciclovir-ion exchange resin DRC particles defined by hydrogen bonding and a Valaciclovir:resin ratio of 1:0.5, a xanthan gum suspending-agent film that decreases interparticle attraction for reconstitution into a homogeneous oral suspension, and a preparation process including complex formation, milling, internal/external phase formulation, and sifting. The claims also include a dissolution/release criterion of more than 95% at 10 minutes in 900 ml HCl 0.1N.
Hydrogen-bonded drug-resin complex particles
Each DRC particle comprises hydrogen bonds between the ion exchange resin and a cationic center of Valaciclovir.
Defined Valaciclovir-to-resin ratio in DRC
The ratio of Valaciclovir to the ion exchange resin in the DRC particle is 1:0.5.
Xanthan gum film decreasing interparticle attraction
The powder comprises xanthan gum as a suspending agent, wherein the suspending agent forms a film around each DRC particle and the film decreases interparticle attraction.
Reconstitution into homogeneous oral suspension
The powder is configured to be reconstituted with an aqueous diluent to form a homogeneous suspension for oral administration.
Dissolution/release profile in HCl 0.1N
More than 95% of Valaciclovir is released from complexation at 10 minutes when suspended in 900 ml HCl 0.1N.
Valaciclovir as the only active pharmaceutical ingredient
Valaciclovir is the only active pharmaceutical ingredient.
Process forming DRC particles and powder
Complexing Valaciclovir with the ion exchange resin, milling the DRC particles to a particle size less than 250 μm, dry mixing the DRC particles with excipients to form an internal phase including xanthan gum and optionally a pH agent, mixing with an external phase, and sifting the powder to eliminate clumps.
The claims are anchored in Valaciclovir-ion exchange resin DRC particles defined by hydrogen bonding and a Valaciclovir:resin ratio of 1:0.5, combined with xanthan gum to form a film that decreases interparticle attraction and supports reconstitution into a homogeneous oral suspension. The formulation is further tied to a dissolution requirement of more than 95% release at 10 minutes in 900 ml HCl 0.1N, and the process claims cover complex formation, milling, internal/external phase formulation, and sifting.
Stated Advantages
Improves reconstitution by forming a homogeneous suspension for oral administration.
Decreases interparticle attraction via a xanthan gum film around DRC particles, supporting resuspendability.
Provides taste masking.
Achieves a dissolution/release profile where more than 95% of Valaciclovir is released from complexation at 10 minutes in 900 ml HCl 0.1N.
Documented Applications
Pediatric oral administration of a reconstitutable powder for suspension, configured to be reconstituted with an aqueous diluent into a homogeneous suspension.
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