Data di Pubblicazione:
2018
Citazione:
Poly(sodium methacrylate, methyl methacrylate) to design highly loaded orodispersible films / U.M. Musazzi, F. Selmin, P. Minghetti, F. Cilurzo. ((Intervento presentato al 11. convegno World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology tenutosi a Granada nel 2018.
Abstract:
INTRODUCTION
In the design of a new technological platform for orodispersible films (ODF), the following aspects have to be considered. First, ODF should exhibit suitable mechanical properties to overcome the tensile stress generated during the manufacturing procedures. Secondly, ODF should disintegrate in few minutes as well as other orodispersible dosage forms. Thirdly, the stickiness of ODF should be also avoided to favour the patients’ handling. As a matter of fact, polymers used to design ODF are highly hygroscopic materials that can become sticky upon exposure to the ambient humidity [1].
This work aims to evaluate the use of poly(sodium methacrylate, methyl methacrylate) (NaPMM) [2] to design ODF prepared by casting technique, using PEG400 as plasticizer. The impact of the polymer/plasticizer ratio and the residual water content on film properties was investigated using placebo ODF. Moreover, the drug loading capacity of the ODF was assessed using ketoprofen (KP) and paracetamol (PAR), as model drugs.
MATERIALS
NaPMM was prepared salifying a 15% w/w Eudragit®S100 (Evonik Industries, G) aqueous suspension with sodium hydroxide [2]. KP (MIAT S.p.A., I); PAR (Farmalabor, I); PEG400 and Tween®80 (Carlo Erba Reagenti, I); Span®80 (Croda, E).
METHODS
ODF preparation
The casting solutions were obtained adding PEG400 to the NaPMM solution in different polymer/plasticizer ratio (90/10 - 40/60 % w/w). In drug-loaded ODF, active ingredients were added to the slurry to reach a final concentration of 25%, 50% w/w for KP and 50%, 70% w/w for PAR. The dispersion was cast at the rate 1 m/min over a silicone release liner to obtain film thickness of about 100 μm (Mathis LTE-S(M), CH). The drying conditions were set to vary the different residual water content in ODF.
Films were cut and packed in individual airtight seal packs using a triple layer film and stored at 25±1 °C until use.
ODF characterization
The residual water content of ODF was expressed as loss of drying (LOD), which was determined gravimetrically using a thermobalance and (Gilbertini, I) keeping samples at 105 °C until constant weight.
ODF stickiness was evaluated by thumb tack test and probe tack test.
Mechanical properties
Flexibility: the test was carried out by bending a ODF over an 8-mm mandrel. Films were considered flexible if no cracks over the bending area were visible at a 5x magnification.
Tensile properties: the test was conducted according to ASTM D882-02 test using an Instron 5965 texture analyser, equipped with a 50 N load cell (Instron, UK). Initial grip separation and crosshead speed were 40 mm and 12.5 mm/min, respectively. The tensile strength (σmax), percent elongation at break () and Young’s modulus (Y) were determined for each sample.
Disintegration test
The disintegration test was carried out in water on 2x3 cm sample using a Ph. Eur. apparatus.
ATR-FTIR spectroscopy
The ATR-FTIR spectra of raw Eudragit®S100 and drug loaded ODF were collected over the wavenumber region 4000–650 cm−1 (32 runs) using a SpectrumTMOne spectrophotometer (PerkinElmer, USA).
RESULTS
Placebo ODF, containing PEG400 in the 10-30 % w/w range and 10-15 % w/w of LOD, were homogeneously transparent in appearance, easy-to-handle and able to disintegrate within 30 s. Non-sticky films were obtained only for PEG400 content lower than 40% w/w (Table 1). At higher concentrations, the ODF stickiness increased with the residual water content. In particular, the probe tack test evidenced that, at the highest LOD value in ODF plasticized by 40% w/w of PEG400, the maximum detachment stress should not exceed 12±2 kPa to assure a film ease to handle.
Figure 1 exemplifies the possible tensile patterns of placebo ODF. At low strain values, a linear r
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
U.M. Musazzi, F. Selmin, P. Minghetti, F. Cilurzo
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