Penicillin suspension

In many circumstances it may be difficult to mask the unpleasant taste of the active ingredient. Regardless of flavoring used, parents consistently report that children prefer cephalosponin products to penicillin suspensions [98],... 

Clarithromycin has been compared with amoxicillin suspension in the treatment of children with lower respiratory tract infections. No significant differences were seen between the groups with respect to clinical cure rates and incidence and severity of adverse events, which generally were mild [35], Five days of treatment with clarithromycin suspension was superior to 10 days of penicillin suspension in eradicating Streptococcus pyogenes in children with streptococcal pharyngitis [36]. 

A suspension of 6-aminopenicillanic acid (36.4 grams) in water was adjusted to pH 7.2 by the addition of N aqueous sodium hydroxide and the resulting solution was treated with a solution of 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride (46.1 grams) in isobutyl methyl ketone. The mixture was stirred vigorously for hours and then filtered through Dicalite. The layers were separated and the isobutyl methyl ketone layer was shaken with saturated brine. Then, precipitation of the sodium salt only took place after dilution of the mixture with ether. In this way there was obtained 60.7 grams of the penicillin sodium salt having a purity of 88% as determined by alkalimetric assay. 

Calf kidneys, dog kidneys and rhesus monkey kidneys were treated with trypsin to give suspensions of cells. The suspensions were centrifuged and the packed cells diluted with 400 volumes (calf cells) or 200 volumes (dog cells and rhesus monkey cells) of a growth medium consisting of 5% horse serum and 0.5% lactalbumen hydrolysate in Earle s saline, with 100 units/ml each of penicillin and streptomycin. These media were used separately to produce Semliki Forest/calf interferon, Semliki Forest/dog interferon and Semliki Forest/rhesus monkey interferon. The cell-containing growth medium was dispensed into 500 ml medical flat bottles (70 ml in each). The cultures were incubated at 36°C. Confluent sheets of cells (monolayers) were formed in 5 to 6 days. The growth medium was then removed and the monolayers were washed with isotonic phosphate-buffered saline, pH 7.5. 

This structure is the traditional target for a group of antibiotics which include the penicillins (Chapter 5), but a httle-noticed report which appeared in 1948 showed that low concentrations of disinfectant snbstances cansed cell wall lysis such that a normally tuibid suspension of bacteria became clear. It was thought that these low concentrations of disinfectant cause en mes whose normal role is to synthesize the cell wall to reverse their role in some way and effect its dismption or lysis. 

As mentioned earlier in this chapter, penicillins are very unstable in aqueous solution by virtue of hydrolysis of the p-lactam ring. A successful method of stabilizing penicillins in liquid dosage forms is to prepare their insoluble salts and formulate them in suspensions. The reduced solubility of the drug in a suspension decreases the amount of drug available for hydrolysis. An example of improved stability of a... 

In contrast, parenteral suspensions have relatively low solids contents, usually between 0.5 and 5%, with the exception of insoluble forms of penicillin in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intralesional, intraarticular, or subcutaneous injection. Syringeability is an important factor to be taken into consideration with injectable dosage forms. The viscosity of a parenteral suspension should be sufficiently low to facilitate injection. Common suspending vehicles include preserved isotonic saline solution or a parenterally acceptable vegetable oil. Ophthalmic and optic suspensions that are instilled into the eye/ear must also be prepared in a sterile manner. The vehicles are essentially isotonic and aqueous in composition. The reader should refer to Chapter 12 for further discussion on parenteral products. 

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

Two basic methods are used to prepare parenteral suspensions (a) sterile vehicle and powder are combined aseptically, or (b) sterile solutions are combined and the crystals formed in situ. Examples of these procedures may be illustrated using Penicillin G Procaine Injectable Suspension USP and Sterile Testosterone Injectable Suspension USP. 

A solution of penicillin is not stable beyond two weeks even at refrigerator temperatures. However, the use of suspensions of sparingly soluble amine salts (procaine and hydrabamine salts) in aqueous vehicles allowed marketing of a ready-made penicillin product. 

Ahmed A. K. S. Chasis and B. McBarnette. Petition of the Natural Resources Defense Council Inc. to the Secretary of Health and Human Services requesting immediate suspension of approval of the subtherapeutic use of penicillin and tetracyclines in animal feeds" Nov. 20. NRDC New York NY. 1984. 

NRDC contended that the suspension of these subtherapeutlc uses of penicillin and the tetracyclines In animal feeds poses no human health problem. No potential human health problem has been Identified In the literature. Any risk of eating meat from an animal that becomes 111, because penicillin and the tetracyclines were not available, could be alleviated by using substitute antibiotics and better farming practices to prevent or reduce the Incidence of disease. Moreover, there would be an Increased probability of effectively treating the diseases with therapeutic levels of antibiotics If they were not used at subtherapeutlc levels. 

The BP utilises formation of a derivative in order to quantify penicillins in formulations. Some penicillins do not have distinctive chromophores a further problem with these molecules is that when they are in suspensions they are not readily extracted away from excipients since they are quite insoluble in organic solvents which are immiscible with water. Using the formation of a complex with the mercuric ion in the presence of imidazole as a catalyst, a derivative of the penicillin structure is produced, which has an absorption maximum between 325 and 345 nm. In the assay, comparison with pure standard for the particular penicillin is carried out rather than relying on a standard A(l%, 1 cm) value. This assay is used by the BP for... 

Penicillins are available in tablets, chewable tablets, capsules, powder for oral suspension, powder for injection, prefilled syringes for injection, premixed dextrose solutions for injection, and solutions for infusion. 

In aqueous suspensions, the particle size is the important factor for their stability, dissolution and absorption of drug e.g. sulphadimethoxine when given in suspension form is absorbed much quickly as compared when given in tablet form. Penicillin V, when given in aqueous suspension gives much higher initial blood level as compared to the tablets or capsules. 

Buckwalter FJ, Dickison HL. The effect of vehicle and particle size on the absorption, by the intramuscular route, of procaine penicillin G suspension. J Am Pharm Assoc Sci Ed 1958 47 661. 

Kollidon 17 PF is eminently suitable for improving the wetability of the active substance in parenteral suspensions, e.g. penicillin ampoules. It reduces the sedimentation rate and improves the dispersability. Kollidon 17 PF, in the amounts used for this purpose, exerts practically no influence on the viscosity. 

An example of the second approach is penicillin G procaine suspensions, where an increase in the particle size resulted in prolongation of the therapeutic level (0.03 unit/mL) from 24 hours for particles at 1 to 2 am to more than 72 hours for particles at 150 to 250 pm.23... 

The temperature rose to 26°C and as reaction proceeded the free acid form of the penicillin separated as a white solid. After 30 minutes the suspension was cooled to 10°C and stirring was continued at this temperature for 1 hour more. The mixture was then cooled to 0°C, centrifuged, and the solid product washed with aqueous acetone (250 ml) and finally dried in an air oven at 30°C. The product (440 grams, 94%) had [a]D20 +106.3° (c 1 in EtOH) and was shown by alkalimetric assay to be 97.5% pure. 

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