Tablet freeze drying

Breaking points are the availability of the raw materials and primary containers of reliable suppliers, the feasibility of analysis of the drug substance and the preparation and the availability of equipment. As an example, preparation processes such as tableting, freeze-drying or aseptic production are accessible in a few pharmacies. The preparation of oral solids with controlled release is not possible in pharmacies mainly to lacking equipment (fluidised-bed techniques and instrumental analysis, etc). Working with radiopharmaceuticals also requires very specific facilities, as is the case with preparation of solid dosage forms with hazardous substances. 

The hydration state of risedronate sodium was monitored continuously in a fluidized bed dryer and correlated to data on the physical stability of tablets made from the monitored material [275]. The final granulation moisture was found to affect the solid-state form, which in turn dictated the drug s physical stability over time. The process of freeze-drying mannitol was monitored continuously with in-line Raman and at-line NIR spectroscopies [276]. The thin polymer solvent coatings, such as poly(vinyl acetate) with toluene, methanol, benzene, and combinations of the solvents, were monitored as they dried to generate concentra-tion/time profiles [277]. 

In the Penzyme test, freeze-dried Streptomyces oo-carboxypeptidase is placed in sealed vials to which the milk sample is added. A preliminary incubation is carried out for 5 min at 47 C to cause some inactivation of the enzyme molecules. The degree of inactivation is dependent on the amount of -lactams presumed to be present in the milk sample. Subsequent addition of a reagent tablet containing synthetic o-alanine oligopeptide and o-amino acid oxidase followed by reincubation at 47 C for 15 min results in the release of o-alanine, its amount... 

The Aria test is a routine assay in which a heat-treated milk sample is added to a well of a microtiter plate containing a freeze-dried tablet containing Bacillus subtilis ATCC 6633, nutrients, and triphenyltetrazoliumchloride as redox indicator (33). Following incubation, the normal growth of the organism is inhibited if antibacterials are present, and the uncolored indicator is not reduced into its red form. Detection of sulfonamides requires prior addition of trimethoprim in the milk samples analyzed. 

Vaginal tablets containing lactobacilli have been used in order to restore the normal vaginal flora. Formulation of these delivery systems requires specific proceedings in order to provide viability of lactobacilli and stability of the final product. Freeze drying of bacterial suspensions has been tested to obtain lyophilized powders for tablet production [81]. These powders were shown to be processable and tablet production was easy and reproducible. Also, the use of double-layer tablets (fast-release layer and slow-release layer) seems to be an interesting approach to lactobacilli administration. 

Zydis system A freeze-dried, porous tablet Enhanced oral bioavailability Maxalt-MLT (Rizatriptan benzoate) ... 

Although excipients are the non-active ingredients, they are indispensable for the successful production of acceptable solid dosage forms. The important roles played by excipients in tablets and capsules, freeze-dried, and spray-dried powders, as well as powder aerosol formulations, were discussed. Some recent applications of excipients in controlled, release formulations for biologicals were also highlighted. Finally, incompatibility problems attributable to excipients were considered with an emphasis on the indirect role of excipients through moisture distribution. 

The term moisture, usually defined as wetness conferred by an unidentified liquid, is assumed here to be due to water. Thus, the scope of this article is the characterization of and consequences due to relatively small amounts of water associated with solids of pharmaceutical interest. Chemical stability, crystal structure, powder flow, compaction, lubricity, dissolution rate, and polymer film permeability are some properties of pharmaceutical interest that have been demonstrated to be influenced by the presence of moisture. Wet granulation, extrusion, spheronization, tray drying, freeze drying, spray drying, fluid-bed drying, tableting, and aqueous film coating are some unit operations that obviously depend on the amount and state of water present. 

Dissociation of HCl or HBr from drug salts may occur, resulting in the release of the hydrohalide gas.f These gases in turn may interact with excipients or corrode tableting tooling. Such dissociation with gas loss may be induced and/or facilitated by processing, e.g., freeze-drying. 

Fig. 39 Instantaneously soluble freeze-dried medicament platelets/tablets. Cross-sectional side view and top view (A), border line between the surface (upper part), and the cross-section (lower part of the picture) (B), inner part of the platelet (C).

Sanchez, L. Torrado, S. Lustres, J.L. Gelatinized/freeze-dried starch as excipient in sustained release tablets. Int. J. Pharm. 1995, 115, 201-208. 

Corveleyn S, Remon JP. Stability of freeze-dried tablets at different relative humidities. Drug Dev Ind Pharm 1999 25(9) 1005-1013. 

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