[A phaeochromocytoma in a Lhasa Apso dog]. / Een phaeochromocytoom bij een Lhasa Apso.

This report describes a case of phaeochromocytoma in an intact male Lhasa Apso dog of nearly 10 years old. The dog was suffering from acute lethargy and vomiting. After a successfully performed surgery and concurrent medication, to restore a temporary Addison s disease, the dog is doing clinically well six months later without any remaining symptoms.

An improved in vitro method for the evaluation of antacids with in vivo relevance.

An improved in vitro method for the evaluation of antacids for use with standard equipment is described. The method is a modification of an older method (RIGO method) and has in vivo relevance. The improved method uses USP dissolution test apparatus 2 with a stirring rate of 125 rpm in combination with a computerized automatic burette. The test solution is 250 ml 0.02 M HCl. A total of 20 min after addition of an antacid to the test solution titration starts at a constant speed of 2.0 ml/min 0.1 M HCl. The proposed acceptance criteria for a waiver for clinical studies are: pH after 4 min not less than 2.5 to ensure a rapid onset of effect, pH after 20 min not exceeding 7.0 to ensure that the pH in the stomach remains within physiological values, buffering capacity between pH 2.5 and 4.5 not less than 8 meq/dose and neutralizing capacity not less than 10 meq/dose to ensure sufficient efficacy within the physiological range. The improved method has been validated with respect to robustness to variations in sample preparation, repeatability and intermediate precision and has been cross-validated versus the RIGO method. The improved method has been found to be rather insensitive to variations in sample pretreatment and at least equivalent to the RIGO method.

Disintegration of sublingual tablets: proposal for a validated test method and acceptance criterion.

In the Netherlands the market share of isosorbide dinitrate 5 mg sublingual tablets is dominated by 2 products (A and B). In the last few years complaints have been received from health care professionals on product B. During patient use the disintegration of the tablet was reported to be slow and/or incomplete, and ineffectiveness was experienced. In the European Pharmacopoeia (Ph. Eur.) no requirement is present for the disintegration time of sublingual tablets. The purpose of this study was to compare the in vitro disintegration time of products A and B, and to establish a suitable test method and acceptance criterion. A and B were tested with the Ph. Eur. method described in the monograph on disintegration of tablets and capsules as well as with 3 modified tests using the same Ph. Eur. apparatus, but without movement of the basket-rack assembly. In modified test 1 and modified test 2 water was used as medium (900 ml and 50 ml respectively), whereas in modified test 3 artificial saliva was used (50 ml). In addition, disintegration was tested in Nessler tubes with 0.5 and 2 ml of water. Finally, the Ph. Eur. method was also applied to other sublingual tablets with other drug substances on the Dutch market. With modified test 3 no disintegration could be achieved within 20 min. With the Ph. Eur. method and modified tests 1 and 2 product A and B differed significantly (p < 0. 001), with product B having longer disintegration times. These 3 methods were capable of discriminating between products and between batches. The time measured with the Ph. Eur. method was significantly lower compared to modified tests 1 and 2 (p < 0.001) and correlated well with the Nessler tube results. It is concluded that the in vivo complaints on product B could be related to the in vitro data. Furthermore, it is proposed that for immediate release of sublingual tablets the disintegration time should be tested. The Ph. Eur. method is considered suitable for this test. In view of the products currently on the market and taking into consideration requirements in the United States Pharmacopeia and Japanese Pharmacopoeia, an acceptance criterion of not more than 2 min is proposed.