Abstract
Celecoxib (Celebrex®) is the only widely used NSAID that selectively inhibits the COX-2 isoenzyme. Celebrex® is absorbed slowly in the fasted state and food intake further delays absorption. In this work, an amorphous water dispersible granule formulation of celecoxib is described with in vitro characterization, preclinical and clinical data. The formulation exhibited very high passive permeability and apparent solubility, significantly outperforming the micronized celecoxib and the drug product Celebrex®. The granule formulation remained stable for at least 1 year in stability tests. In dog studies, tmax was 1 h with over 50% of Cmax reached within 15 min regardless of food intake. A phase 1 clinical trial was conducted with 12 volunteers at 100- and 200-mg doses. Celecoxib plasma concentrations reached 250 ng/ml, the effective therapeutic plasma level, in less than 15 min regardless of food or dose. The novel celecoxib formulation is rapidly absorbed, demonstrating the potential utility as an acute treatment offering advantages over the currently marketed product.
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Abbreviations
- CI:
-
Confidence interval
- Cmax :
-
Maximal plasma concentration
- AUC:
-
Area under the concentration curve
- COX:
-
Cyclooxygenase
- ECG:
-
Electrocardiography
- FaSSIF:
-
Fasted state simulating intestinal fluid
- FeSSIF:
-
Fed state simulating intestinal fluid
- GI tract:
-
Gastrointestinal tract
- GMR:
-
Geometric mean ratio
- HPMC:
-
Hydroxypropylmethylcellulose
- IMP:
-
Investigational medicinal product
- LOQ:
-
Limit of quantification
- MS:
-
Mass spectrometry
- NSAID:
-
Non-steroidal anti-inflammatory drug
- PES:
-
Polyethersulfonate
- PiB:
-
Powder in bottle
- PVDF:
-
Polyvinylidene fluoride
- PVP:
-
Polyvinylpyrrolidone
- S:
-
Solubility
- SAE:
-
Serious adverse event
- SDS:
-
Sodium dodecyl sulfate
- SGF:
-
Simulated gastric fluid
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Angi, R., Solymosi, T., Erdősi, N. et al. Preparation, Pre-clinical and Clinical Evaluation of a Novel Rapidly Absorbed Celecoxib Formulation. AAPS PharmSciTech 20, 90 (2019). https://doi.org/10.1208/s12249-018-1270-2
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DOI: https://doi.org/10.1208/s12249-018-1270-2