Stability data Size of formulations and measured values Direct compression

BASF Fine Chemicals Generic Drug Formulations 1998

1.6 Stability data

It is only in exceptional cases or when certain groups of active substances are present that data are given on the chemical and or the physical stability of the formulations. The reasons are as follows. a. The formulations are practically always modified by the customer when they are scaled up to meet the demands of industry. b. Aromas or colorants are added to the formulations in amounts depending on the particular taste of the target group. c. In view of the very number of for- mulations presented here and for capacity reasons, the long-term stability of all of them cannot be checked. The stability of the preparation may change as a result of items a. and b. Thus the final formulation must be checked in any event. Data on the chemical stability are often available for sensitive materials, e. g. PVP-iodine or vitamins. They mostly concern either storage at room temperature 20 – 25 °C over a period of one year or a stress test that lasts at least just as long. In a number of formulations, data are also listed on the physical stability. 2 Tablets

2.1 Size of formulations and measured values

The formulations were developed on a laboratory scale in which case 200 –1,000 g of the mixtures to be tabletted were used. Normally, the amounts weighed out in the formula- tions correspond to the amount in the tablets multiplied by a factor of 1,000. The weight, hardness, disintegration, and chipping of the tablets and the data on their release are measured values.

2.2 Direct compression

The technology involved in direct compression assumes great impor- tance in the tablet formulations, be- cause it is often the cheapest means, particularly in the production of ge- nerics, that the active substance per- mits. The limiting factors are the physical properties of the active sub- stance and its concentration in the tablets cf. Chapter 2.5. Even sub- stances such as ascorbic acid that are hardly suitable for direct tabletting owing to the friability of their crystals can normally be directly pressed into tablets at concentrations of 30 – 40 . However, this technique is not as suitable if the content of ascorbic ac- id is higher. This limit may be shifted upwards by special direct compres- sion auxiliaries, e. g. Ludipress. Two important alternatives, viz. Ludipress and Kollidon VA 64, can be found in the BASF line of pharmaceutical exci- pients for direct compression. A. Ludipress Ludipress is a speciality derived from lactose, Kollidon 30, and Kollidon CL. It thus combines the properties of a filler, binder, disintegrant, and flowability agent and also often acts as a release accelerator. By virtue of its versatility formulations containing it are usually very simple. It can also be combined with almost all active sub- stances with the exception of those that enter into a chemical interaction with lactose Maillard reaction. Active substances, e. g. many anal- getics, behave very differently with Ludipress when the dosage is ex- tremely high. Acetylsalicylic acid and metamizole can be pressed when lit- tle Ludipress has been added; ibu- profen requires a larger amount; and the fraction of Ludipress required in the tablets is too large for paraceta- mol = acetaminophen. B. Kollidon VA 64 An alternative to Ludipress is the out- standing dry binder Kollidon VA 64 together with excipients, e. g. calcium phosphate, microcrystalline cellulose, lactose, or starch, and a disintegrant, e. g. Kollidon CL. This combination even allows 500 mg of paracetamol to be pressed into good tablets with a weight of 700 mg. No other dry binder has a binding power and plasticity comparable to those of Kollidon VA 64. Plasticity, in particular, is an important parameter in direct compression. As can be seen in Fig. 1, this property of Kolli- don VA 64 is not adversely effected by increasing the pressure. The bene- ficial properties of Kollidon VA 64 can BASF Fine Chemicals Generic Drug Formulations 1998 BASF Fine Chemicals Generic Drug Formulations 1998 also be exploited for the production of concentrated active substance that is subsequently used for direct tabletting. Obviously, Kollidon VA 64 and Ludi- press can also be combined with one another.

2.3 Wet granulation