Effect of solubility enhancement on nasal absorption of meloxicam

Abstract

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 T value (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.

Formulation and comparison of spray dried non-porous and large porous particles containing meloxicam for pulmonary drug delivery

“…MX exhibits a pH dependent solubility: in buffers at pH 7.4-7.7 MX demonstrates almost 43 fold solubility (1.74±0.2 mg/mL, 37 °C) at this pH than in distilled water (0.04±0.01 mg/mL, 37 °C) (Horváth et al, 2016). Due to this characteristic, MX was dissolved at room temperature (18-20 °C) at higher pH, stabilized with 1 M sodium hydroxide aqueous solution, to prepare a stock solution for the spray drying.…”

Modifying the physicochemical properties of NSAIDs for nasal and pulmonary administration

“…Based on literature data, meloxicam as a preferential selective COX-2 inhibitor could be a new candidate for nasal application to induce rapid-onset analgesia. For an enhanced nasal absorption, its salt form, meloxicam potassium monohydrate has been investigated [14]. Both in vitro and in vivo results indicate that this salt form is preferable for the development of an intranasal liquid dosage form.…”

Investigation of the Absorption of Nanosized lamotrigine Containing Nasal Powder via the Nasal Cavity

“…In some cases the aim was to formulate nanosystems, that may be advantageous due to reduced particle size and increased particle surface, which can affect the absorption positively [25]. Our research group has also successfully formulated nanosized meloxicam and meloxicam potassium monohydrate containing nasal spray formulation for nasal drug delivery [26,27].…”