Lyophilized formulated dose

Case Study Reference Standard Compared with a Lyophilized Formulated Dose In this case study, calibrators for an immunoassay were prepared from a lyophilized formulated dosage material for a therapeutic protein, and compared with the corresponding liquid formulation reference standard. Spiked control samples were likewise prepared from both sources of material and run in the... 

FIGURE 9.1 A comparison of two calibration curves, one prepared from the reference standard and another from the lyophilized formulated dose. The reference standard was provided as a frozen aqueous solution. Each was spiked into assay buffer and dilutions were made to provide the corresponding calibrators with the same concentrations. 

Each vial contains the non radioactive materials necessary to prepare one patient dose, which is a sterile, lyophilized formulation, containing 1.25 mg of Arcitumomab and 0.29 mg of stannous chloride per vial, with potassium sodium tartrate tetrahydrate, sodium acetate trihydrate, sodium chloride, acetic acid, glacial, hydrochloric acid, and sucrose. Technetium Tc 99 m Arcitumomab, is formed by reconstitution of the contents of this vial with 30 mCi of Tc 99 m sodium pertechnetate in 1 mL of sodium chloride for injection, LISP. 

In a pharmacokinetic-based study by Hedin et al. [94], hGH was administered with a nasal permeation enhancer, sodium tauro-24,25-dihydrofusidate (STDHF), in patients deficient in growth hormone (GH) using a reprocessed lyophilized form of hGH. The lyophilized material was formulated with STDHF and all the subjects received the formulation by both the nasal and subcutaneous routes. The dose given by the subcutaneous route was a standard dose of O.lIU/kg body weight (BW), whereas three different doses (of 0.2,0.4, and 0.8 IU/kg BW) of the nasal formulation were given. As compared with the subcutaneous route, all three nasal formulations showed a rapid increase in the plasma levels of hGH, with Y rn ix being reached 15-25 min after administration, as compared with 3-4 h in the case of the subcutaneous route. However, the Cmax was higher in the case of the latter route, and the nasal formulations touched baseline after 3-4 h, as compared with 14-18 h after subcutaneous delivery. 

Crystalline cellulose, hydroxypropyl cellulose, and Carbopol 934 have been studied in combination with lyophilized insulin as bioadhesive powder dosage forms for nasal delivery. Each formulation tested resulted in an decrease in plasma glucose level after nasal administration in dog and rabbit models. The most effective formulation, crystalline cellulose blended with insulin, decreased the plasma glucose level to 49% of the control value. In ternary systems the lyophilized Carbopol 934 and insulin blend with crystalline cellulose powder has been the most effective, leading to a hypoglycemia on the order of one-third of the effect obtained after intravenous injection of the same dose of insulin. The plasma glucose levels obtained in the volunteers after administration of the insulin-Carbopol-crystalline cellulose powder formulation were quite variable [38],... 

For delicate drug formulations, the industry offers a modified unit-dose system. The lyophilized ingredi-ent(s) are stored separately from the solvent. Prior to administration, the drug formulation is reconstituted and ready to be dispensed. 

There is a wide range of devices available to suit different applications. Some are ideally suited to chronic injections of varying doses of insulin several times a day, others are more suited to weekly dosing of the same dose of a therapeutic protein or even a monoclonal antibody. Still others will be capable of conveniently reconstituting lyophilized drug formulations... 

Cisplatin is only available for intravenous use. It is generally supplied in vials as a solution or as a lyophilized powder. The possibility exists for dermal, oral, or inhalation exposure during production, and during preparation of dosing formulations. 

Formulations will increasingly become more complex as the content of the antibiotic is raised within the liposomes [91], and stability is a general concern Dispersions may exhibit aqueous stability of only a matter of days. This issue has partially been addressed through the use of reconstituted lyophilized preps, and a formulation of anamycin has demonstrated over 3 months stability in the solid state [56]. Beauloac et al. [58] have taken this one step further by aerosolizing a dry powder of lyophilized liposome-tobramycin to administer to mice infected with Pseudomonas aeruginosa. [58]. However, the use of powdered preparations does not address the dosing problem. 

Clinical Use. Vancomycin and teicoplanin as formulated dmgs are lyophilized powders to be reconstimted with sterile water for injection. Vancomycin hydrochloride [1404-93-9], is presented in vials of 500 mg that give 100—200 mL solution of pH 2.5—4.2. It is administered by slow (60 min) infusion at a dose of 500 mg every 6 h or 1 g every 12 h/d The teicoplanin contains the five factors (87%) plus 13% of the pseudoaglycone T-A3-1. It is presented in vials containing 200 mg of lyophilized power that after dissolution with 3 mL of solvent gives a solution at pH 7.5. The dose regimen is 200—800 mg/d by iv bolus administration. 

---