Suspensions sterile

Many dry solid parenteral products, such as the cephalosporins, are prepared by sterile crystallization techniques. Control of the crystallization process to obtain a consistent and uniform crystal form, habit, density, and size distribution is particularly critical for drug substances to be utilized in sterile suspensions. For example, when the crystallization process for sterile ceftazidime pentahydrate was modified to increase the density and reduce the volume of the fill dose, the rate of dissolution increased significantly. 

Sterile suspensions can be challenging with respect to physical stability, and this should be reflected in the... 

Oils have been used as vehicles for several topical eyedrop products that are extremely sensitive to moisture. Tetracycline HC1 is an antibiotic that is stable for only a few days in aqueous solution. It is supplied as a 1% sterile suspension with Plastibase 50W and light liquid petrolatum. White petrolatum and its combination with liquid petrolatum to obtain a proper consistency is routinely used as the vehicle for ophthalmic ointments. 

The rHBsAg is produced in an engineered S. cerevisiae strain and is likely purified subsequent to fermentation by a procedure somewhat similar to that presented in Figure 13.10. The final product is presented as a sterile suspension of the antigen absorbed onto aluminium hydroxide (adjuvant), in either single-use vials or pre-filled syringes. It also contains NaCl and phosphate buffer components as excipients. It is intended for i.m. injection, usually as 10 pg in a volume of 0.5 ml for infants/children or 20 pg (in 1.0 ml) for adults. The normal dosage schedule entails initial administration followed by boosters after 1 and 6 months. 

The drug is commercially available as the acetate ester, being esterified at the hydroxy methyl group (at C21). It is formulated as oral tablets (dosage strengths of 5 mg, 10 mg, and 25 mg), or as a parenteral sterile suspension (50 mg/mL) for intra-muscular administration. 

System (1) has been adopted by the USP [71] for the assay of cortisone acetate and its official pharmaceutical formulations (either sterile suspension or tablets). The standard is prepared by transferring about 12 mg of cortisone acetate RS, accurately weighed, into a glass-stoppered 50-mL conical flask. 25.0 mL of internal standard solution is added, and the solution sonicated for 5 minutes. Approximately 1 mL of this solution is combined with 3 mL of mobile phase to obtain the standard preparation. The column is any 25 cm x 4.6 mm column that contains packing L3. The... 

Intra-arterial Afferential organs Sterile suspension for injection... 

Structural Formula Sterile suspension, in a buffered water medium, of... 

Content uniformity for tablets, capsules, sterile solids, and sterile suspensions. A common deficiency is the use of different analytical methodologies for uniformity and for assay purposes without supporting their equivalency or adequately defining correction factors. 

Betaxolol is suppUed as a sterile suspension of 0.25% betaxolol HCl (Betoptic-S). The suspension is a unique formulation containing a polyacrylic acid polymer (carbomer 934P) and a cationic exchange resin, which is beUeved to increase the drug residence time in the eye (see Chapter 2). This product is the racemic compoimd, preserved with 0.01% BAC, and approved for twice-daily use. 

With sterile suspensions, the active drug ingredient is suspended in a liquid carrier before administration. 

Sterile suspensions (injectable and ophthalmic) have characteristics that are not commonly shared by other suspension systems, such as ease of resuspension, drainage, absence of foreign particulate matter and pyrogens, and syringeability in the case of injectable suspensions. 

Various procedures for the manufacture of sterile suspensions have been reported by Akers et al. Grimes,and Portnoff. " At present, there is no pharmaceutically acceptable chemical agent that can be added to the finished suspension to make it both sterile and safe. Therefore, an elaborate program of sterility checks at critical phases of the operation is required. 

Grimes, T.L. Scaleup and Manufacture of Sterile Suspensions. APhA 133rd Annual Meeting, San Francisco, March 19, 1986. 

Sterile Corticotropin Zinc Hydroxide Suspension, USP. Sterile corticotropin zinc hydroxide suspcnsi a a sterile suspension nf corticotropin, adsorbed on zinc hy droxide. which contains no lc.ss than 4. > and no more llun 33 fig of zinc fnr each 20 USP corticoiropin units. BccaiK of its prolonged uctiviiy due to slow rclca.se nf corticotropin, an initial dnse of 40 U.SP units cun be admini.steted inltamg.v... 

A unique approach to minimizing tissue residues and thus withdrawal periods is used with Pfizer s ceftiofur product Excenel Sterile Suspension for bovine respiratory disease. This one-time administered Oh-based suspension is injected into the middle section of the ear. During slaughter the ears of cattle are not put into the food chain. The product is also used for swine, but for that species is given intramuscularly. 

Tetanus toxoid and tetanus toxoid adsorbed (adsorbed onto aluminum hydroxide, phosphate, or potassium sulfate to increase antigenicity) are sterile suspensions of the toxoid derived from C. tetani. Both toxoids are used to promote active immunity against tetanus however, tetanus toxoid adsorbed is the preferred agent because it elicits a greater immune response and is associated with fewer adverse reactions. 

C. Vaccine. Vaccination with the FDA Licensed, currently available, killed suspension of V. cholerae provides about 50% protection that lasts for no more than 6 months. Vaccine consists of sterile suspension of equal parts of phenol-killed Ogawa and Inaba serotypes of V. cholerae. The initial dose is two injections given at least 1 week apart with booster doses every 6 months. This cholera vaccine does not prevent transmission of infection. It is not recommended by the World Health Organization (WHO) or the DoD. 

Injectable preparations are usually either sterile suspensions or solutions of a drug in water or in a suitable vegetable oil. Solutions act faster than drugs in suspensions with an aqueous vehicle, providing faster action than an oleaginous vehicle. Drug absorption occurs... 

Insulin Zinc Suspension. Lente Insulin Lente lie-tin Insulin Novo Lente Human Monotard Insulin Ultra -card Lentard Monotard Semitard Ultratard. Sterile suspension, in a buffered water medium, of insulin modified by the addition of zinc chloride in a manner such that the solid phase of the suspension consists of a mixture of crystals and amorphous materia] in a ratio of approx 7 3 Hallas -Moller, Lancet 267, 1029 (1954). Contains 40 Or 80 U.S.P, insulin units/ml. Prepn of amorphous zinc insulin suspension Petersen et aL, U.S. pat, 2 82,203 (1959 to Novo Terapeu-tisk Lab. A IS). 

The drug is a sterile suspension of Zinc-insulin crystals and protamine sulphate in buffered water for injection, usually combined in such a fashion that the solidphase of the suspension essentially comprises of crystals composed of insulin, protamine and zinc. 

It is invariably obtained as a sterile suspension of insulin in buffered water for injection, carefully modified by the addition of zinc chloride (ZnCl2) in such a maimer that the solid-phase of the suspension comprises of a mixture of crystalline as well as amorphous insulin present approximately in a ratio of 7 portions of crystals and 3 portions of amorphous substance. Each mL is obtained from sufficient insulin to provide either 40, 80, or 100 USP Insulin Units of the Insulin Activity. 

The drug is a sterile suspension of insulin in buffered water for injection, that has been adequately modified by the addition of zinc chloride (ZnCl2) and protamine sulphate. The protamine snlphate... 

There also is a marketed Lyme disease vaccine containing recombinant OspA (31,115,116). The vaccine is a sterile suspension of a noninfectious recombinant vaccine containing an immunodominant outer surface protein of Borrelia burgdorferi known as lipoprotein OspA. The antigen is adsorbed onto aluminum hydroxide as an adjuvant. Vaccine efficacy against definite Lyme disease is 78% after three doses. 

Solutions are undoubtedly the most commonly used and accepted forms. They are relatively simple to make, filter and sterilize. Suspensions, while not as common as solutions, are widely used for formulations involving anti-inflammatory steroids (e.g., prednisolone alcohol and acetate). Early resistance to Aese forms, based on the emotional fear that "particles in the eye are bad", has largely been overcome as particle sizes have been reduced, and as the benefits of these dosage forms have been demonstrated. 

However, inherent in these methods are the assumptions that no chro-mogenic substances, other than adrenaline, are present and that the rotatory power of the solutions is due solely to /-adrenaline which precludes their use for routine testing of samples in which the nature of the other materials present is unknown. For such samples Welsh has produced a method in which the adrenaline is converted quantitatively to the triacetyl derivative which may be determined qualitatively as well as quantitatively by polarimetry, and this method has been adopted by the U.S.P, for Epinephrine Solution, Inhalation, Injection, and Sterile Suspension and Epinephrine Bitartrate Ophthalmic Ointment. It is described in detail under Solution of Adrenaline. 

Injection of Bismuth Oxychloride, B.P. A sterile suspension containing 10 per cent of bismuth oxychloride with sodium chloride and chlorocresol. 

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