Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug
Introduction
Most pharmaceutical dosage forms for oral administration are formulated to be swallowed or chewed in order to deliver the drug. Pediatric and geriatric patients may have difficulties swallowing or chewing these tablets. Tablets that rapidly dissolve upon contact with saliva in the buccal cavity could present a solution to those problems and so there is an increased interest in fast dissolving dosage forms for buccal, sublingual and oral administration. Oral lyophilized products combine the properties of freeze-dried dosage forms as fast reconstitution, good preservation and stability, with the benefits of liquid dosage forms for bioavailability (Jaccard and Leyder, 1985).
In this study, the influence of different formulation and process parameters on the characteristics of lyophilized oral dosage forms was investigated. Maltodextrins, gelatins, xanthan gum and hydroxyethylcellulose were evaluated as possible excipients in the formulation of freeze-dried tablets. Additionally dissolution experiments were performed using hydrochlorothiazide (HCT) as a model drug. HCT was chosen as a poorly soluble drug because the objective was to look at the influence of structure disruption of lyophilised tablets in the presence of `suspended' material.
Section snippets
Materials
The spray dried maltodextrins (Eridania-Beghin Say-Cerestar, Vilvoorde, Belgium) were obtained by enzymatic hydrolysis of corn starch, and had different dextrose equivalents (D.E.): C(PUR01910 (D.E.=14), C(PUR01921 (D.E.=22), C(PUR01934 (D.E.=38). Xanthan gum (Ludeco, Brussels, Belgium) and Idroramnosan® (hydroxyethylcellulose 2% w/v: 5800 mPa.s) (Ludeco, Brussels, Belgium) and different gelatins (PB Gelatins, Vilvoorde, Belgium): hydolysed gelatins Solugel® LB (Bloom value 10–30 g) and
Results and discussion
Rapidly dissolving tablets can be an interesting oral dosage form for geriatric and pediatric patients. The effectiveness of a sublingual piroxicam fast dissolving dosage form based on lyophilisation has been reported (Auvinet et al., 1995). The choice of the binding agent is an important parameter in the formulation of these products. In a formulation study using lactose as a filler, Vennat et al. (1993)reported that the best results in disintegration time of lyophilised tablets were obtained
Acknowledgements
The authors wish to thank Eridania-Béghin Say-Cerestar (Vilvoorde, Belgium) for the generous supply of the maltodextrins and for the use of the texture analyser. The gelatins were kindly provided by PB Gelatins (Vilvoorde, Belgium). Prof. Wettinck (Lab. Non-Ferrometallurgie, University of Gent, Belgium) is kindly acknowledged for the use of the Scanning Electron Microscope.
References (12)
- Auvinet, B., Crielaard, J.M., Manteuffel, G.E., Mueller, P., 1995. A double blind comparison of piroxicam...
- Chiba, Y., Kohri, N., Iseki, K., Miyazaki, K., 1991. Improvement of dissolution and bioavailability for mebendazole, an...
- Corveleyn, S., Remon, J.P., 1996. Maltodextrins as lyoprotectants in the lyophilisation of a model protein, LDH. Pharm....
- Dawson, P.J., Hockley, D.J., 1991. Scanning electron microscopy of freeze-dried preparations: relationship of...
- Her, L., Nail, S.L., 1994. Measurement of glass transition temperatures of freeze-concentrated solutes by differential...
- Jaccard, T.T., Leyder, J., 1985. Lyoc: a new pharmaceutical form. Ann. Pharm. Fr. 43,...