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
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12453732-B2
Publication Date
2025-10-28
Expiration Date
Abstract
A process for preparing a powder for reconstitution as a suspension includes the following steps: First, complexing Valaciclovir with an ion exchange resin and forming Drug-Resin complex (DRC) particles. The complexing includes Dry blending of Drug:Ion Exchange Resin in a ratio 1:0.8 to form a blend;Kneading the blend with water in a ratio of Drug:Ion Exchange Resin:Water 1:0.8:0.5 to form a wet mass;Drying of the wet mass at 40° C. Next, milling of the Drug-Resin complex particles until particle size gets less than 250 μm, and then dry mixing of the Drug-Resin complex particles with excipients to form an internal phase. The excipients of the internal phase comprise a suspending agent and a pH agent, and the suspending agent forms a film around each DRC particle and the film decreases interparticle attraction. Next, mixing the internal phase with excipients of an external phase to form the powder, and then sifting the powder to eliminate any clumps.
Core Innovation
The invention relates to a pediatric oral suspension powder comprising valaciclovir or a pharmaceutical acceptable salt or derivative thereof and an ion exchange resin, where valaciclovir is complexed with the ion exchange resin to form drug-resin complex (DRC) particles. Each DRC particle comprises hydrogen bonds between the ion exchange resin and a cationic center of valaciclovir, and the ratio of valaciclovir to the ion exchange resin within the DRC particle is 1:0.5-1:0.8.
The process includes mixing the DRC particles with xanthan gum as a suspending agent and optionally a pH agent. The suspending agent forms a film around each DRC particle, and the film decreases interparticle attraction.
The powder is reconstituted with an aqueous diluent to form a homogenous suspension for oral administration. The disclosure also reports selection and optimization of ion exchange resins and valaciclovir-to-resin ratios, together with evaluation of palatability/appearance, impurity trends, dissolution in HCl 0.1N, and stability under accelerated conditions.
Claims Coverage
The independent claim family covers a process for preparing an oral suspension powder and reconstituting it for oral administration, with three inventive features.
Drug-resin complex particle formation at a defined ratio
Complexing valaciclovir with the ion exchange resin to form drug-resin complex (DRC) particles comprising hydrogen bonds between the ion exchange resin and a cationic center of valaciclovir, where the ratio of valaciclovir to the ion exchange resin within the DRC particle is 1:0.5-1:0.8.
Film-forming dispersion with xanthan gum to decrease interparticle attraction
Mixing the DRC particles with a suspending agent which is xanthan gum and optionally a pH agent, wherein the suspending agent forms a film around each DRC particle and the film decreases interparticle attraction.
Defined release performance in HCl 0.1N
The powder reconstituted with an aqueous diluent to form a homogenous suspension for oral administration, wherein the powder comprises a dissolution profile where more than 95% of valaciclovir is released from complexation with the ion exchange resin at 10 minutes when suspended in 900 ml HCl 0.1N.
Overall, the claim coverage centers on DRC formation by hydrogen-bond interactions at a specified valaciclovir-to-ion-exchange-resin ratio, followed by dispersion with xanthan gum (optionally with a pH agent) to form a film that decreases interparticle attraction, producing an oral suspension powder that meets a dissolution/release criterion in HCl 0.1N at 10 minutes.
Stated Advantages
More than 95% valaciclovir release from complexation with the ion exchange resin at 10 minutes when suspended in 900 ml HCl 0.1N.
A film formed by xanthan gum around DRC particles that decreases interparticle attraction.
Reconstitution yields a homogenous suspension for oral administration.
Documented Applications
Pediatric oral administration of a reconstituted homogenous suspension prepared from a powder comprising valaciclovir (or pharmaceutical acceptable salt or derivative) and an ion exchange resin.
Interested in licensing this patent?