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SecundumArtem Current & Practical Compounding Information for the Pharmacist. STABILITY OF EXTEMPORANEOUSLY PREPARED PEDIATRIC
FORMULATIONS USING ORA-PLUS WITH
ORA-SWEET AND ORA-SWEET SF - PART III
Loyd V. Allen, Jr., R.Ph. Ph.D., FACA, FAPhA The Ora-Sweet and Ora-Plus products are of defined composition from lot to lot, which is an advantage for Martin A. Erickson, III, R.Ph., FACA, FASCP the compounding pharmacist in assessing chemicaland physical stability of various additives.
A large number of drugs are prepared extempora- Table 1: Initial concentration of the active drugs used neously by pharmacists as oral liquid dosage forms.
in the study.
Extemporaneous compounding of this type usuallyinvolves preparing an oral liquid from a commercially Ora-Plus™, Ora-Sweet™ and available dosage form (tablets, capsules, injections) or Ora-Sweet SF™ are vehicles from the pure drug powder.
that are compatible with many Ora-Plus™, Ora-Sweet™ and Ora-Sweet SF™ are Chloroquine Phosphate drugs. Each vehicle possesses vehicles that are compatible with many drugs. It is unique physicochemical char- important that the drug be stable in the vehicle for the Enalapril Maleate acteristics that determine its proposed duration of storage and administration of the suitability for use with various product. Each vehicle possesses unique physicochem- ical characteristics that determine its suitability for use Quinidine Sulfate with various drugs. These characteristics include pH, viscosity, taste, appearance, presence of preservatives, and stability. The vehicle selected must be compatiblewith the drug and the drug must be stable in the vehi- Capsules were emptied into a mortar and the pow- cle for the proposed duration of storage and der broken up with a pestle. Tablets were thoroughly administration of the product.
comminuted in a mortar with a pestle to obtain a fine The purpose of this study was to determine the powder. A portion of the vehicle was added and physical and chemical stability of extemporaneous oral mixed with the powder to form a uniform paste.
formulations of alprazolam, bethanechol chloride, Additional aliquots of the vehicle were added with chloroquine phosphate, cisapride, enalapril maleate, mixing until the final volume was obtained. Sufficient hydralazine hydrochloride, pyrazinamide, quinidine product was prepared so that triplicate samples for sulfate, rifampin and tetracycline hydrochloride,drugs each vehicle could be placed in plastic containers and commonly prescribed in oral liquid dosage forms. This stored at two different temperatures. The product was stability data enables pharmacists to make informed filled in three separate 120 mL amber plastic (polyeth- professional decisions about vehicle selection and the ylene terephthalate, PETG) "prescription ovals" with assignment of expiration periods.
low density polyethylene foam cap linings and stored This stability data enables at 5˚ and 25˚ C, in the absence of light. Samples (5 mL) STABILITY STUDY DESIGN
pharmacists to make informed were removed initially and after 1, 2, 7, 10, 14, 28, 35 Drug selection for this study was based on the professional decisions about and 60 days. The containers were agitated on a rotat- results of an informal survey mailed to community vehicle selection and the assign- ing mixer for 30 minutes prior to obtaining the sample.
and hospital pharmacies. The products and the con- ment of expiration periods.
The apparent pH was determined initially and after 30 centrations selected for this study are shown in Table 1; and 60 days of storage. The oral liquids were examined they were prepared in Ora-Sweet:Ora-Plus (1:1) and at each sampling time for any change in appearance or Ora-Sweet SF:Ora-Plus (1:1). The sources of the drugs were commercially available dosage forms. The samples were analyzed using validated, stabili- Loyd V. Allen, Jr., Ph.D., Professor and Head, ty-indicating assays. Stability was defined as the Pharmaceutics, University of Oklahoma, HSC College of retention of not less than 90% of the original concentra- Pharmacy, Oklahoma City, OK 73190 and Martin A. tion of the active drug.
Erickson III, R.Ph., Professsional Affairs Manager, PaddockLaboratories, Inc., Minneapolis, MN 55427


STABILITY OF EXTEMPORANEOUS FORMULATIONS
Bethanechol chloride retains at least 92% of the original concentration in Ora-Sweet:Ora-Plus at both temperatures for 60 days, and at least 93% Alprazolam 1 mg/mL of the original concentration in Ora-Sweet SF:Ora-Plus at both tempera- Alprazolam 2 mg Tablets tures for 60 days. These results are similar to those obtained by Gupta and Maswoswe2 who demonstrated almost 100% potency of bethane-chol chloride in solution (1 mg/mL) in vehicles such as simple syrup, Alprazolam 1 mg/mL retained at least 91% of the initial drug con- water, buffer solutions (pH 3.0 to 6.8) over 40 days storage at 25˚C.
centration in both vehicles studied at both room and refrigerated Schlatter and Saulnier3, however, showed products (1 mg/mL) in water temperatures for up to 60 days. Alprazolam is a white to off-white, crys- for irrigation were stable for 40 days when stored at 4˚C at pH of 6.5, but talline powder that is insoluble in water and soluble in alcohol.1 The not stable after that; also, solutions prepared from sterile water for injec- stability of alprazolam may be enhanced by its poor aqueous solubility tion were stable for only 21 days. No reason was given in their study to and its presence in these liquid vehicles in a suspension dosage form.
the observation that the solution prepared from sterile water for injection(pH 5.4) was not as stable as that prepared from sterile water for irriga- Table 2: Percent of the initial concentration of alprazolam (1 mg/mL) tion (pH 6.5). An expiration period of 60 days for tablets in preserved remaining after packaging in plastic prescription containers and storage at water, at a concentration of 0.4 mg/mL and stored in a refrigerator has 5˚C or 25˚C for up to 60 days.
also been reported by another reference4.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) Table 3: Percent of the initial concentration of bethanechol (5 mg/mL) remaining after packaging in plastic prescription containers and storage at5˚C or 25˚C for up to 60 days.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.7.
The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.5.
There was less than 0.5 pH unit change throughout the study.
The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.4.
Bethanechol Chloride 5 mg/mL The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.4.
Bethanechol Chloride 50 mg Tablets There was less than 0.5 pH unit change throughout the study.
The Paddock Solid-to-Liquid Solution The physical and chemical properties ofOra-Plus® and Ora-Sweet® help ensure the stability of compounded oral liquids.
Over 40 formulations have been independentlytested.
Call 1-800-328-5113 to receive copies of thestudies or visit our website,www.paddocklabs.com.
The initial pH of the Ora-Sweet:Ora-Plus mixture was 7.0.
Chloroquine Phosphate 15 mg/mL The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 7.0.
Chloroquine Phosphate 500 mg Tablets There was less than 0.5 pH unit change throughout the study.
Chloroquine phosphate 15 mg/mL retained at least 98% of the ini- Enalapril Maleate 1 mg/mL tial drug concentration in these vehicles studied at both room and Enalapril Maleate 20 mg Tablets refrigerated temperatures for up to 60 days. These results are in agree- ment with a study by Odusote and Nasipuri5 showing the stability ofchloroquine in three syrup formulations over 12 weeks. Their study Enalapril maleate 1 mg/mL retained at least 94% of the initial drug con- used either sucrose syrups or methylcellulose solutions adjusted to a centration in both vehicles studied at both room and refrigerated pH of 4.5 to 4.9, along with preservatives, coloring and other excipients.
temperatures for up to 60 days. Enalapril maleate is a white to off-white Another report mentions stability for at least 30 days for a 25 mg/mL crystalline powder that is soluble in water to the extent of 25 mg/mL and in suspension at a pH of 4-6 for 30 days.6 Also, 20 mg/mL chloroquine alcohol at 80 mg/mL.13 It has pK s of 3 and 5.4 and a reported pH of maxi- in simple syrup was shown to be physically stable after storage at 49˚C mum stability of about 3.14 Above pH 5, an increased rate of decomposition for 63 hours and at -6˚C for 8 hours and returned to room temperature.7 occurs. At room temperature, one report provides t results for 0.5 mg/mL Chloroquine is more stable when protected from light.8 Chloroquine solutions at pH 2 and 5 of 262 and 114 days, respectively.15 Another study phosphate is a white, odorless, crystalline powder with a bitter taste reports on the use of enalapril maleate tablets to prepare an oral liquid in 0.1 that exists in two polymorphic forms. Since it is freely soluble in water, and 1.0 mg/mL concentrations in an isotonic citrate buffer at pH 5.16 The the chloroquine phosphate preparations here were solutions of the products were stable at 5˚C for 90 days but at 25˚C the 0.1 and 1.0 mg/mL active drug.9 The pH of a 1% solution of the drug is 4.5.10 preparations were stable for only 55 and 43 days, respectively. One shouldnote, however, that the buffered pH of 5 was above that of maximum sta- Table 4: Percent of the initial concentration of chloroquine phosphate bility. The preparations of Ora-Plus in this current study had pH values in (15 mg/mL) remaining after packaging in plastic prescription contain- the range of 3.92 to 4.77, somewhat closer to that of maximum stability.
ers and storage at 5˚C or 25˚C for up to 60 days.
Table 6: Percent of the initial concentration of enalapril maleate (1mg/mL) Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) remaining after packaging in plastic prescription containers and storage at 5˚Cor 25˚C for up to 60 days.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.4.
The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.5.
There was less than 0.5 pH unit change throughout the study.
The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.8.
The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.7.
Cisapride 1 mg/mL There was less than 0.5 pH unit change throughout the study.
Cisapride 10 mg Tablets Hydralazine Hydrochloride 4 mg/mL Note: Adjust the pH of the final product to about 7.0 using sodium bicarbonate. Hydralazine Hydrochloride 100 mg Tablets Cisapride 1 mg/mL retained at least 91% of the initial drug concen- tration in both vehicles studied at both room and refrigerated Hydralazine hydrochloride 4 mg/mL was not very stable in any of these temperatures for up to 60 days, when adjusted to a pH of 7. vehicles. In the Ora-Sweet:Ora-Plus, it was only stable for 1 day at 5˚C and Cisapride has been demonstrated by Nahata et al to be stable for at in Ora-Sweet SF:Ora-Plus it was stable for about 5 days (interpolated value) least 91 days of storage at refrigerated temperature and 28 days at at 5˚C. The product was not stable for even a day at 25˚C in the Ora- room temperature. Their study used products formulated with a vehi- Sweet:Ora-Plus vehicles. Hydralazine hydrochloride is a white to cle of methylcellulose 1% and simple syrup.11 Horn and Anderson12 off-white/yellow, crystalline powder that is soluble to the extent of 40 studied a formulation consisting of cherry syrup and propylene glycol mg/mL in water and 2 mg/mL in alcohol. It has a pKa of 7.3 and the com- with the pH adjusted to greater than 6.5 with sodium bicarbonate mercially available injection has a pH in the range of 3.4 to 4.17. The pH of a which showed stability at room temperature for at least 3 weeks. It is 2% aqueous solution is in the range of 3.5 to 4.5.18 Numerous studies have important to adjust the pH to neutral to enhance stability of this prod- been reported on the stability of extemporaneously compounded hydralazine hydrochloride products using various vehicles. Alexander Table 5: Percent of the initial concentration of cisapride (1 mg/mL) reported on a formulation consisting of 1.25 mg/mL hydralazine remaining after packaging in plastic prescription containers and storage hydrochloride in maltitol, edetate sodium, sodium saccharin, methyl- at 5˚C or 25˚C for up to 60 days.
paraben, propylparaben, propylene glycol, orange flavoring and water,using acetic acid to adjust the pH to 3.7.19 The product was relatively stable Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) with less than 2% loss of drug at 5˚C in two weeks and a calculated shelf lifeat 25˚C from accelerated temperature data of about 5.13 days. The same authors found hydralazine hydrochloride to be incompatible with edetate sodium and sodium bisulfite in aqueous solution.
Gupta reported the stability of 1% hydralazine hydrochloride in aqueous vehicles containing various sugars, including dextrose, fructose, lactose and maltose, and showed these sugars to have deleterious effects on the stabili- ty of the drug with losses of 30-70% occuring in 24 hours for samples stored in amber bottles at 24˚C.20 When the drug was mixed in vehicles and the second containing methylcellulose and simple syrup. They containing hydrolyzed sucrose in simple syrup or strawberry found that pyrazinamide in both suspensions exceeded 90% of syrup, losses of 93-95% of the active drug occurred in one day.
their initial concentration throughout the two-month study period Unhydrolyzed 85% sucrose solutions provided a better vehicle at both refrigerated and room temperatures. A study by Seifart, with 1% hydralazine hydrochloride where losses of about 10% Parkin and Donald23 , however, in a vehicle of tragacanth, concen- occurred at 24˚C in seven days. Sorbitol solutions provided better trated chloroform water and water showed stability at 4˚C for 22 stability with only 4 and 8% loss in 21 days at 24˚C. The best sta- days, 24˚C for 19 days and at 40˚C for only 8 days.
bility was found using 0.28 M mannitol, with no drug lossoccurring after 21 days at 24˚C. The hydralazine hydrochloride oral Table 8: Percent of the initial concentration of pyrazinamide (10 liquids in this study were prepared from the commercial tablets, mg/mL) remaining after packaging in plastic prescription containers containing lactose. Lactose, a reducing sugar, can form an osazone, and storage at 5˚C or 25˚C for up to 60 days.
increasing the degradation rate of the hydralazine.21 For hydralazine, it may be more appropriate to only prepare suf- Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) ficient product for 24 hours at a time for the patient. Another alternative would be to dispense it in such a manner that it can bemixed immediately prior to administration, i.e., pulverizing the commercial tablets and pre-filling single doses in individual cap- sules. The caregiver could be counseled to empty the contents of asingle capsule into one teaspoonful of vehicle for administration.
Although not ideal, it may enhance positive patient outcomes.
Table 7: Percent of the initial concentration of hydralazine hydrochlo- The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.4.
ride (4 mg/mL) remaining after packaging in plastic prescription The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.5.
containers and storage at 5˚C or 25˚C for up to 60 days.
There was less than 0.5 pH unit change throughout the study.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) Quinidine Sulfate 10 mg/mLRx Quinidine Sulfate 200 mg Tablets Quinidine sulfate retained at least 97% of the original potency in Ora-Sweet:Ora-Plus and 96% in Ora-Sweet SF:Ora-Plus vehicles at both temperatures over the 60 day study period.
The stability of quinidine sulfate has been reported as 30 days at The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.4.
refrigerated temperatures in two vehicles, one consisting of simple The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 4.3.
syrup and the other consisting of 10-12.5% ethanol in citric acid There was less than 0.5 pH unit change throughout the study.
Table 9: Percent of the initial concentration of quinidine sulfate (10 Pyrazinamide 10 mg/mL mg/mL) remaining after packaging in plastic prescription containers Pyrazinamide 500 mg Tablets and storage at 5˚C or 25˚C for up to 60 days.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) Pyrazinamide retains at least 97% of the original concentration in Ora-Sweet:Ora-Plus and 98% in Ora-Sweet SF:Ora-Plus at bothtemperatures for 60 days. The current results for pyrazinamide are supported by a study in different vehicles by Nahata, Morosco and Peritore22. These investigators reported on the stability of pyrazi-namide 100 mg/mL in two vehicles: one containing simple syrup CONGRATULATIONS to Alan Vogenberg, R.Ph., Levittown, PA– winner of the recent Mortar & Pestle
YES, I would like to enter the current Secundum Artem Mortar & Pestle Drawing.
& Pestle!
1. How many prescriptions do you compound per month? _ 2. What powders do you use in your compounding? BRC today!
Pharmacy Address SA6.2 8/97
centration in Ora-Sweet:Ora-Plus at both temperatures for 28 days The initial pH of the Ora-Sweet:Ora-Plus mixture was 3.9.
and in Ora-Sweet SF:Ora-Plus at 5˚C for 10 days, 25˚C for 7 days. It The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 3.9.
should be recommended that the oral liquid tetracycline preparation There was less than 0.5 pH unit change throughout the study.
be prepared from the tetracycline base powder. The problem maybe one of solubility. For example, tetracycline hydrochloride has an aqueous solubility of about 100 mg/mL.28 If tetracycline base is Rifampin 25 mg/mL used, its solubility in water is only about 0.4 mg/mL. At a concen- Rifampin 300 mg Capsules tration of 25 mg/mL in the vehicles used in this study, the tetracycline hydrochloride was in solution. If the base was used, theproduct would be a suspension, with greater stability and a longer Rifampin retained potencies for only 28 days at both tempera-
stability period. The hydrochloride salt was used in this study tures of at least 91% in Ora-Sweet:Ora-Plus and 90% in Ora-Sweet because the tetracycline hydrochloride capsules are the most easily SF:Ora-Plus. The 28 day stability of rifampin in the vehicles in this available form of the drug and the information was needed.
study are similar to other studies. Allen25 reported on 1% rifampinsuspensions prepared using either simple syrup, wild cherry syrup Table 11: Percent of the initial concentration of tetracycline (25 or Syrpalta™ where a 4 week stability at refrigeration temperatures mg/mL) remaining after packaging in plastic prescription containers was suggested. Krukenberg et al26 also recommended a 4 week and storage at 5˚C or 25˚C for up to 60 days.
period in their study of 1% rifampin suspensions formulated usingsyrup NF, simple syrup (Humco), simple syrup (Whiteworth), wild Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) cherry syrup and Syrpalta and storage at both room and refrigerat- ed temperatures. Nahata27 reported that the preparation methodcan influence the dispersion of the drug in the vehicle. There was a difference depending upon whether the product was preparedfrom the capsules or the parenteral solution. He reported a stability of 56 days in syrup for products stored in the refrigerator.
Table 10: Percent of the initial concentration of rifampin (25 mg/mL) remaining after packaging in plastic prescription containers and stor-age at 5˚C or 25˚C for up to 60 days.
The initial pH of the Ora-Sweet:Ora-Plus mixture was 2.6.
The initial pH of the Ora-Sweet SF:Ora-Plus mixture was 2.7.
There was less than 0.5 pH unit change throughout the study.
Ora-Sweet:Ora-Plus (1:1) Ora-Sweet SF:Ora-Plus (1:1) Physical observations, including visual and olfactory obser- vations, did not reveal any substantial changes during the storage time for any of the formulations.
Alprazolam 1 mg/mL, bethanechol chloride 5 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL.
enalapril maleate 1 mg/mL, pyrazinamide 10 mg/mL andquinidine sulfate 10 mg/mL can be compounded extempora- The initial pH of the Ora-Sweet:Ora-Plus mixture was 4.8.
neously from capsules or tablets using Ora-Sweet:Ora-Plus The initial pH of the Ora-Sweet SF:Or--Plus mixture was 4.6.
(1:1) and Ora-Sweet:Ora-Plus SF (1:1) vehicles and are stable There was less than 0.5 pH unit change throughout the study.
for 60 days when stored in the absence of light at both 5˚ and25˚C.
Hydralazine hydrochloride 4 mg/mL was only stable at 5˚ C Tetracycline Hydrochloride 25 mg/mL for one day in Ora-Sweet:Ora-Plus and two days in Ora-Sweet Tetracycline Hydrochloride 500 mg Capsules #6 SF:Ora-Plus. Rifampin 25 mg/mL extemporaneously prepared in these vehicles can be stored for up to 28 days at both storage tem-peratures. Tetracycline hydrochloride 25 mg/mL, however, was Tetracycline hydrochloride retained at least 90% of the initial con- NO POSTAGE
IF MAILED
BUSINESS REPLY MAIL
FIRST-CLASS MAIL PERMIT NO. 6837 MINNEAPOLIS MN Postage will be paid by addressee 3940 Quebec Ave NMinneapolis MN 55427 only stable in Ora-Sweet:Ora-Plus for 28 days at both temperatures; in Analytical Profiles of Drug Substances. Vol. 16, Washington DC: Ora-Sweet SF:Ora-Plus for 10 days in the refrigerator and 7 days at American Pharmaceutical Association; 1987: 207- room temperature; and in cherry syrup, for only 7 days in the refrig- 16. Boulton DW, Woods DJ, Fawcett JP et al. The stability of an erator and 2 days at room temperature. It is recommended that the
enalapril maleate oral solution prepared from tablets. Aust J Hosp tetracycline base powder be used when preparing tetracycline oral liquid.
Pharm. 1994; 24:151-6.
17. McEvoy GK, Ed. AHFS Drug Information 97. Bethesda MD, American Society of Health-System Pharmacists, 1997, p 1390-3.
McEvoy GK, Ed. AHFS Drug Information 97. Bethesda MD, 18. Fbudavari S. Ed. The Merck Index, 12th Ed. Whitehouse Station American Society of Health-System Pharmacists, 1997, pp 1806-7.
NJ, Merck & Co., Inc. 1996, p 815. Gupta VD, Maswoswe J. Stability of bethanechol chloride in 19. Alexander KS, Pudipeddi M, Parker GA. Stability of oral liquid dosage forms. Int J Phar Comp 1997;1:(in process).
hydralazine hydrochloride syrup compounded from tablets. Am J Schlatter JL, Saulnier JL. Bethanechol chloride oral solutions: Hosp Pharm 1993; 50:683-6.
Stability and use in infants. Ann Pharmacother 1997; 31:294-6.
20. Gupta VD, Stewart KR, Bethea C. Stability of hydralazine Extemporaneous Oral Liquid Dosage Forms. Toronto, Ontario: hydrochloride in aqueous vehicles. J Clin Hosp Pharm. 1986; 11:215- Canadian Society of Hospital Pharmacists; 1988:3.
Odusote MO, Nasipuri RN. Effect of pH and storage conditions 21. Halasi S, Nairn JG. Stability of hydralazine hydrochloride in on the stability of a novel chloroquine phosphate syrup formulation.
parenteral solutions. Can J Hosp Pharm. 1991;43:237-41.
Pharm Ind 1988; 50:367-9.
22. Nahata M, Morosco RS, Peritore SP. Stability of pyrazinamide Anon. Extemporaneous Oral Liquid Dosage Preparations.
in two suspensions. Am J Health-Syst Pharm. 1995;52:1558-60.
Toronto, Ontario. Canadian Society of Hospital Pharmacists; 23. Seifart HI, Parkin DP, Donald PR. Stability of isoniazid, rifampin and pyrazinamide in suspensions used for the treatment of Closson RG. Liquid dosage form of chloroquine. DICP 1988; 22: tuberculosis in children. The Ped Inf Dis J. 1991:10:826-31.
24. Extemporaneous Oral Liquid Dosage Forms. Toronto, Ontario: Hong DL. Chloroquine Phosphate. In: Florey K, ed. Analytical Canadian Society of Hospital Pharmacists; 1988:21.
Profiles of Drug Substances.Vol. 5, Washington DC: American 25. Allen Jr LV. Rifampin suspension. U.S. Pharmacist 1989;14:102- Pharmaceutical Association; 1976: 61-85.
McEvoy GK, Ed. AHFS Drug Information 97. Bethesda MD, 26. Krukenberg CC, Mischler PG, Massad EN, Moore LA, Chandler American Society of Health-System Pharmacists, 1997, p 557.
AD. Stability of 1% rifampin suspensions prepared in five syrups.
10. Fbudavari S. Ed. The Merck Index, 12th Ed. Whitehouse Station Am J Hosp Pharm. 1986; 43:2225-8.
NJ, Merck & co., Inc. 1996, p 2220.
27. Nahata MC, Morosco RS, Hipple TF. Effect of preparation 11. Nahata MC, Morosco RS, Hipple TF. Stability of cisapride in a method and storage on rifampin concentration in suspensions. Ann liquid dosage form at two temperatures. The Annals of Pharmacotherapy 1995; 29:125-6.
28. McEvoy GK. AHFS Drug Information-97. Bethesda MD, 12. Horn JR, Anderson GD. Stability of an extemporaneously com- American Society of Health-System Pharmacists, 1997:384.
pounded cisapride suspension. Clinical Therapeutics 1994;16:169-172.
13. McEvoy GK, Ed. AHFS Drug Information 97. Bethesda MD,American Society of Health-System Pharmacists, 1997, pp 1234-1244.
14. Fbudavari S. Ed. The Merck Index, 12th Ed. Whitehouse StationNJ, Merck & Co., Inc. 1996, p 3610.
15. Ip DP, Brenner GS, Enalapril Maleate. In: Florey K, ed.
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Postgrad Med J 2001;77:759–764 Hypokalaemia and hyperkalaemia A Rastergar, M Soleimani compartments. Humans, as carnivorous ani- Disturbances in potassium homoeostasis mals, consume large amount of potassium presenting as low or high serum potas- intermittently. Dietary potassium, which is sium are common, especially among hos-

As listed in the compendium of pharmaceuticals and specialties (cps)

As listed in the Compendium of Pharmaceuticals and Specialties (CPS) Immunocal® Protein isolate Glutathione Precursor Immunotec Pharmacology IMMUNOCAL is a natural source of the glutathione precursor cysteine for the maintenance of a strong immune system. It is fat-free and contains less then 1% lactose and has a high protein biological value (>110 BV) providing all essential amino acids. The systemic availability of oral glutathione is negligible; the vast majority of it must be manufactured intracellularly from precursors. Glutathione is a tripeptide made intracellularly from its constituent amino acids L-glutamate, L-cysteine and glycine. The sulfhydryl (thiol) group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Provision of this amino acid is the rate-limiting factor in glutathione synthesis by the cells since bioavailable cysteine is relatively rare in foodstuffs. Furthermore, cysteine if ingested as the free amino acid L-cysteine, has toxic potential and is spontaneously catabolized in the gastrointestinal tract and blood plasma. Toxicity is avoided when cysteine is integrated into larger proteins such as serum albumin, alpha lactalbumin and lactoferrin. IMMUNOCAL is a bovine whey protein isolate specially prepared to provide a rich source of bioavailable cysteine. Following digestion, the cysteine remains as the stable form cystine (2 molecules of cysteine linked by a disulfide bond) and glutamylcystine. After absorption, these dipeptides travel safely in the blood stream and readily enter the cells to release free cysteine for intracellular glutathione synthesis. IMMUNOCAL is a cysteine delivery system. The disulphide bond in cystine is pepsin and trypsin resistant but may be split by heat, low pH or mechanical stress, releasing free cysteine. When subject to heat or shearing forces (inherent in most extraction processes), the fragile disulfide bonds within the peptides are broken and the bioavailability of cysteine is greatly diminished.