Effect of solubility enhancement on nasal absorption of meloxicam.
Besides the opioids the standard management of the World Health Organization suggests NSAIDs (non-steroidal anti-inflammatory drugs) alone or in combination to enhance analgesia in malignant and non-malignant pain therapy. The applicability of NSAIDs in a nasal formulation is a new approach in pharmaceutical technology. In order to enhance the nasal absorption of meloxicam (MX) as an NSAID, its salt form, meloxicam potassium monohydrate (MXP), registered by Egis Plc., was investigated in comparison with MX. The physico-chemical properties of the drugs (structural analysis, solubility and dissolution rate) and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out to determine the nasal applicability of MXP as a drug candidate in pain therapy. It can be concluded that MX and MXP demonstrated the same equilibrium solubility at the pH5.60 of the nasal mucosa (0.017mg/ml); nonetheless, MXP indicated faster dissolution and a higher permeability through the synthetic membrane. The animal studies justified the short Tmaxvalue (15min) and the high AUC of MXP, which is important in acute pain therapy. It can be assumed that the low mucoadhesivity of MXP spray did not increase the residence time in the nasal cavity, and the elimination from the nasal mucosa was therefore faster than in the case of MX. Further experiments are necessary to prove the therapeutic relevance of this MXP-containing innovative intranasal formulation.
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary; Goodwill Pharma Ltd., Szeged, Hungary.
Tamás
T
Horváth
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
Rita
R
Ambrus
Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary.
Gergely
G
Völgyi
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
Mária
M
Budai-Szűcs
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Árpád
Á
Márki
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
Péter
P
Sipos
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
Csilla
C
Bartos
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Adrienn B
AB
Seres
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Anita
A
Sztojkov-Ivanov
Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary.
Krisztina
K
Takács-Novák
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
Erzsébet
E
Csányi
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Róbert
R
Gáspár
Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary. Electronic address: revesz@pharm.u-szeged.hu.
Piroska
P
Szabó-Révész
D000281:Administration, Intranasal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D065588:Nasal Absorption / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility / Q000187:drug effects; D013843:Thiazines / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam
In vivo test; Meloxicam; Meloxicam potassium monohydrate; Mucoadhesion; Nasal formulation; Side-Bi-Side™ model; Solubility