Dear Colleagues;
This week, in our series of preparations used in the treatment of anal fissures, we will continue with the formula HYDROPHILE GLYCEROLTRINITRAT-REKTALCREME 0.2 % (NRF 5.10.), which is prepared with nitroglycerin and is frequently prescribed nowadays.
This formula is interesting as it was the subject of an article in the Marmara Pharmacy Journal. In the research article titled ‘’Evaluation of pharmacy-prepared (compounded) nitroglycerin ointments in terms of content and presentation characteristics’’ conducted in Turkey, 568 pharmacies—primarily in Adana, followed by Ankara, Izmir, and Trabzon—were contacted to prepare this formula. Only 38 of them (6.7%) confirmed that they could prepare a compounded nitroglycerin ointment prescription. However, when visiting the pharmacies, despite the phone confirmation of feasibility, medication could only be prepared in 23 pharmacies (4%), with reasons given such as the active ingredient being out of stock at the warehouse, that it could only be prepared after the weekend, or that there was a misunderstanding over the phone. If you wish, let us read what follows directly from the lines of the journal that published the research:
‘’Unfortunately, the contents, patient presentation formats, and galenic characteristics of these products prepared in pharmacies cannot be routinely inspected. In this study, it was aimed to determine the amount of nitroglycerin in samples obtained from pharmacies that prepared the compounded nitroglycerin (0.4%) ointment prescription. Compounded medicines prepared in pharmacies constitute a negligible proportion of total drug consumption. Today, it is prescribed as a compounded drug… In addition, whether these medicines prepared in pharmacies were presented to the patient with appropriate packaging and labeling was also evaluated. In our study, while only 6.7% of the pharmacies contacted declared that they could prepare the 0.4% nitroglycerin ointment, only 4% were actually able to prepare it when visited. None of the medicines assumed to be prepared by pharmacies according to the prescription met the required 0.4% content; in fact, 9 samples contained active substance below measurable values (0.008%), and the highest nitroglycerin ratio in the samples was found to be 0.24%, well below the acceptable limits (0.36-0.44%). In the analysis, only all three samples of the licensed pharmaceutical preparation named Rectogesic® were found to be within acceptable limits in terms of nitroglycerin quantity. Furthermore, it was determined that the information required on a medicine package/box was also missing. Finding a pharmacy that will prepare nitroglycerin ointment and the time required to prepare this medicine hinders the patient’s access to the medication. In case of access, the insufficient content of the drug leads to a loss of time in patient treatment, prolongation of disease exposure, and ultimately constitutes an unacceptable situation by impairing the right to receive treatment. For this reason, it is evident that there is a need for regular inspection of compounded medicines prepared in pharmacies.’’
Returning to our formula;
As written in prescriptions in Germany,
HYDROPHILE GLYCEROLTRINITRAT-REKTALCREME 0.2 % (NRF 5.10.)
Ölige Glyceroltrinitrat-Lösung 5% ……………………. 4.0 g
Basiscreme DAC ………………………………………….. zu 100.0 g
As can be understood from the formula, while glycerol trinitrate, which constitutes the active substance, is provided to pharmacies in Germany as an Oily nitroglycerin solution (nitroglycerin solution containing 5% medium-chain triglycerides), it can be obtained from suppliers in our country as a 1% solution in ethanol. Likewise, while a hydrophilic base cream formulation is preferred as the vehicle in Germany, physicians in our country mostly prefer a vaseline/lanolin aa. mixture.
Glycerol Trinitrate – Nitroglycerin – Trinitroglycerin: It has a vasodilatory effect. Undiluted glyceryl trinitrate is a dense, flammable, explosive liquid ranging in color from white to light yellow. Diluting its 1% alcoholic solution with an equal volume of water yields a clear solution; diluting it with twice its volume of water forms a cloudy mixture consisting of glyceryl trinitrate that precipitates upon standing; careless handling of this mixture may cause an explosion. CAUTION! Undiluted glyceryl trinitrate may explode upon impact or excessive heat. Therefore, it must be isolated in very small quantities. In late December 2004, the FDA did not approve a 0.2% topical nitroglycerin ointment evaluated for the treatment of pain associated with anal fissures and hemorrhoids. However, in most clinical trials conducted in children, topical nitroglycerin ointments were found to be effective in the treatment of anal fissures.
Preparation – Modus operandi:
The article in the Marmara Pharmacy Journal states regarding this formula that less active ingredient than required was found in the preparations compounded in pharmacies. Therefore, when preparing the formula, we must not overlook the fact that calculations must be carried out meticulously.
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Accordingly, assuming that the prescription received by our pharmacy is written as follows;
Glyceryl trinitrate ……………… 0.2% g
Vaseline
Lanolin ……………………………../ aa 25 g
According to this formula, the calculation should be as follows:
Preparation of 50 g of 0.2% nitroglycerin ointment;
The density of the Glycerol trinitrate solution in 1000 ml of 1% ethanol solution obtained from supplier companies is in the range of 0.80-0.82. To obtain the 100 mg of Glycerol trinitrate required in the formula, we need 10 cc of Glycerol trinitrate solution in 1% ethanol.
The calculated 10 cc of NG is added gradually and incorporated into the lanolin softened on a heating plate, and then vaseline softened on the heating plate is added and the preparation is stirred with a glass rod until a homogeneous mixture is obtained.
0.2% NITROGLYCERIN OINTMENT (STARTING FROM 1% STOCK SOLUTION):
In 1000 grams 2 g
In 50 grams X g
X = 0.10 grams = 100 mg nitroglycerin
Amount to be taken from the 1% stock solution:
In 100 ml 1 g nitroglycerin
In X ml 0.10 g nitroglycerin
X = 10 ml stock solution (density = 0.8)
Stock solution amount = 0.8 x 10 ml = 8.0 grams of stock solution will be used.
Nitroglycerin ……………. 100 mg (8.0 g of 1% stock solution to be taken)
Lanolin (Anhydrous) ……… 17.0 g (Stock solution will first be absorbed by lanolin)
Vaseline (White) ……… 25 g (Lanolin mixture will be blended with vaseline)
A total of 50 grams of ointment will be packaged and labeled.
Usage: Used in the treatment of acute and chronic anal fissures. A pea-sized amount of cream is applied twice daily after defecation around the anal verge, ensuring it is not inserted too deeply.
Wishing you a good week…
I would like to express my gratitude to my dear colleague Pharmacist Anooshirvan Miandji for his contribution to the formula.
Spec. Pharm. Ahmet Nezihi Pekcan
Pekcan Pharmacy – Konya
[email protected]
Tel: (332) 3520657
http://www.majistralformul.com/
