Pharmaceutical agents containing diphosphonic acids and salts th

Details Pharmaceutical agents containing diphosphonic acids and salts th Pharmaceutical agents containing diphosphonic acids and salts th

1995-02-24

1997-09-02

Azpuru, Carlos A.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Implant or insert

A61F 202

Patent

active

056629184

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/EP93/02217.
The invention concerns well-tolerated injection solutions that are stable when stored in primary packaging made of glass and contain at least one diphosphonic acid or at least one physiologically acceptable salt of such an acid, processes for producing these solutions and the use of polyethylene glycols to stabilize these solutions.
Diphosphonic acids within the sense of the present invention are compounds which have already been introduced some time ago into therapeutic practice for the treatment of disorders of calcium metabolism.
These compounds are of particular interest for the treatment of hypercalcaemia and are used as active substances in therapeutic agents for the treatment of osteoporosis and in tumour osteolysis. The efficacy of disphosphonates (sodium etidronate, dichloromethylene-diphosphonate, aminohydroxypropane-, aminohydroxybutane-aminohydroxypentane-, aminohydroxyhexane-diphosphonate, and others) in inhibiting bone-reabsorption which is increased in an unnatural manner in many bone diseases such as e.g. Morbus Paget, in bone tumours, in bone metastases, in osteoporosis or in hyperparathyroidism, has already been known for a long time.
Diphosphonates as pharmaceutical agents are described for example in EP 0 170 228; EP 0 197 478; EP 0 224 751; EP 0 252 504; EP 0 252 505; EP 0 258 618; EP 0 350 002; EP 0 273 190; WO 90/00798.
Solid forms of administration for pharmaceutical agents containing diphosphonates in the form of preparations containing effervescents are described in DE 3 500 670.
Diphosphonic acids and salts thereof are in principle readily soluble in water and are usually quite stable substances with regard to temperature influences. In the production of injection solutions which had been adjusted to the pH value of blood (pH value 7.4), the solutions unexpectedly became turbid on longer storage despite the good solubility of the active substances. In addition it turned out that the content of active substance in the injection solutions in the glass vessels became continuously lower on storage over a long period of time even when the solutions did not yet exhibit any turbidity. The reasons for this reduction is the content of active substance are unclear.
Injection solutions are usually filled into primary packaging made of glass (e.g. ampoules, vials, ready-to-use syringes, carpoules) in which case the glass ampoules used for pharmaceutical purposes are usually composed of glasses of hydrolytic class I. The chemical stability of glass vessels for pharmaceutical use is assessed by determining soluble, mineral substances that are released into water under standardized conditions. In this process the contact of the water with the inner surface of the vessel or with powdered glass is stipulated. The hydrolytic resistance is determined by titrating the hydroxide ions that are formed in the solution. The glass vessels are classified into four types of glass according to their hydrolytic resistance. Glass of class I is composed of neutral glass with a high hydrolytic resistance due to the chemical composition of the glass as such. Glass of class II is usually composed of soda-lime-silicate glass and has a high hydrolytic resistance due to appropriate surface treatment. Glass of class III is usually composed of soda-lime-silicate glass and has a medium hydrolytic resistance. Glass of class IV is composed of soda-lime-silicate glass and has a low hydrolytic resistance.
Despite the use of glass containers of hydrolytic class I it was established that the content of aluminium ions in the injection solutions continuously increased on longer storage.
Due to these three disadvantageous findings on longer storage of the solutions--turbidities, reduction in the content of active substance and increase of the aluminium content--such solutions must be labelled as being physically unstable with regard to the intended official licence and registration as pharmaceutical agents. In addition it is also undesirable from a medical point of view to administer

REFERENCES:
patent: 4645762 (1987-02-01), Biere et al.
patent: 4687767 (1987-08-01), Bosies et al.
patent: 4902679 (1990-02-01), Benedict et al.

Affiliated with

Also associated with

Rating

Pharmaceutical agents containing diphosphonic acids and salts th does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Pharmaceutical agents containing diphosphonic acids and salts th, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical agents containing diphosphonic acids and salts th will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-306245