Parenteral administration requirements

Parenteral administration requires sterile products. Aseptic production, filtration, y-irradiation, and heating are normally used to achieve sterility. Filtration sterilization of dispersed systems requires high pressure and is not applicable to particles larger than 0.2 pm. 

The liquid formulation for parenteral administration requires additional physical and microbiological functionalities, such as syringeability, sterility, osmolarity, and pyrogen freedom. The particle size change can influence the syringeability of injection of a suspension formulation as well as the level of irritation at the site. Terminal sterilization such as autoclave or gamma irradiation may affect the physical stability of the dosage form. Both formulation and container systems should be evaluated [63]. 

Oral administration requires great care because some patients have difficulty swallowing (because of a dry mouth or other causes). Other patients may refuse to take the drug. If the patient refuses to take the drug, the nurse contacts the primary health care provider regarding this problem because parenteral administration of the drug may be necessary. 

As has been pointed out earlier in this chapter, the dietary consumption and historical medicinal use of carotenoids has been well documented. In the modern age, in addition to crocin, 3.7, and norbixin, 3.8, several carotenoids have become extremely important commercially. These include, in particular, astaxanthin, 3.6 (fish, swine, and poultry feed, and recently human nutritional supplements) lutein, 3.4, and zeaxanthin, 3.3 (animal feed and poultry egg production, human nutritional supplements) and lycopene, 3.2 (human nutritional supplements). The inherent lipophilicity of these compounds has limited their potential applications as hydrophilic additives without significant formulation efforts in the diet, the lipid content of the meal increases the absorption of these nutrients, however, parenteral administration to potentially effective therapeutic levels requires separate formulation that is sometimes ineffective or toxic (Lockwood et al. 2003). 

Classic beri-beri, rarely seen in the United States and Europe, except in alcoholism (P4), is endemic in the Far East because of the prevalent diet of decorticated rice (F6). It occurs in two forms wet beri-beri, characterized by edema and cardiovascular symptoms (G6), and dry beri-beri with peripheral neuritis, paralysis, and atrophy of the muscles. Conditions which may predispose to deficiency by increasing thiamine requirements are pregnancy (see section 2.4), and lactation, hyperthyroidism, malignant disease, febrile conditions, increased muscular activity, high carbohydrate diets, and parenteral administration of glucose solutions. A constant supply of thiamine is required for optimal nutrition because storage in the liver and elsewhere is limited. Thiamine is synthesized by bacteria in the intestinal tract of various animals, but this is not a dependable source for man. 

Among the disadvantages of the LMWP strategy for the treatment of chronic renal disease are the requirement for parenteral administration and the possible immunogenicity of the... 

Since parenteral administration is required, drug targeting formulations should provide distinct advantages in efficacy and safety compared with the non-targeted drug... 

Inject subcutaneously or IM when possible. In older children and adults, inject IM in the upper outer quadrant of the buttocks. In infants and young children, the anterolateral aspect of the thigh or the deltoid region is preferred. When IV administration is unavoidable, inject very slowly, not exceeding 1 mg/min. Anticoagulant-induced prothrombin deficiency in adults 2.5 to 10 mg or up to 25 mg (rarely, 50 mg) initially. Determine subsequent doses by prothrombin time (PT) response or clinical condition. If in 6 to 8 hours after parenteral administration (or 12 to 48 hours after oral administration), the PT has not been shortened satisfactorily, repeat dose. If shock or excessive blood loss occurs, transfusion of blood or fresh frozen plasma may be required. 

Determine initial route of administration by the severity of symptoms. With only the earliest manifestations of diabetic gastric stasis, initiate oral administration. If symptoms are severe, begin with parenteral therapy. Administer 10 mg IV over 1 to 2 minutes. Parenteral administration up to 10 days may be required before symptoms subside, then oral administration may be instituted. Reinstitute therapy at the earliest manifestation. 

Which route of administration is optimum Choosing the optimum dmg administration route takes into account the specific circumstances of each individual case. For example, can the patient tolerate oral medications, or is intravenous administration required Does the patient have venous access For how long can it be maintained Is intramuscular administration a possibility In many clinical situations, the available formulation determines the route of administration. Antibiotics are a prime example of this phenomenon ceftriaxone, for example, is available only for parenteral administration while amoxicillin is administered orally. 

Glucocorticoids are available in a wide range of preparations, so that they can be administered parenterally, orally, topically, or by inhalation. Obviously the oral route is preferred for prolonged therapy. However, parenteral administration is required in certain circumstances. Intramuscular injection of a water-soluble ester (phosphate or succinate) formed by esterification of the C21 steroid alcohol produces peak plasma steroid levels within 1 hour. Such preparations are useful in emergencies. By contrast, acetate and tertiary butylacetate esters must be injected locally as suspensions and are slowly absorbed from the injection site, which prolongs their effectiveness to approximately 8 hours. 

Some of the dosage formulations available for protein pharmaceuticals are listed in Table 5.7. An examination of Table 5.7 reveals that no protein drug up until this time has been formulated for oral administration. Most protein drugs are administered by means of injection (parenteral administration). Parenteral administration includes intravenous, intra-arterial, intracardiac, intraspinal or intrathecal, intramuscular, intrasynovial, intracuta-neous or intradermal, subcutaneous injections, and injection directly into a dermal lesion (e.g., a wart). The parenteral route of administration requires a much higher standard of purity and sterility than oral administration. It also may require trained... 

Aspirin (acetylsalicylic acid, Figure 7.9) is a derivative of salicyclic acid, which was first used in 1875 as an antipyretic and antirheumatic. The usual dose for mild pain is 300-600 mg orally. In the treatment of rheumatic diseases, larger doses, 5-8 g daily, are often required. Aspirin is rapidly hydrolysed in the plasma, liver and eiythrocytes to salicylate, which is responsible for some, but not all, of the analgesic activity. Both aspirin and salicylate are excreted in the urine. Excretion is facilitated by alkalinisation of the urine. Metabolism is normally very rapid, but the liver enzymes responsible for metabolism are easily saturated and after multiple doses the terminal half-life may increase from the normal 2-3 h to 10 h. A soluble salt, lysine acetylsalicylic acid, with similar pharmacological properties to aspirin, has been used by parenteral administration for postoperative pain. Aspirin in low doses (80-160 mg daily) is widely used in patients with cardiovascular disease to reduce the incidence of myocardial infarction and strokes. The prophylaxis against thromboembolic disease by low-dose aspirin is due to inhibition of COX-1-generated thromboxane A2 production. Because platelets do not form new enzymes, and COX-1 is irreversibly inhibited by aspirin, inhibition of platelet function lasts for the lifetime of a platelet (8-10 days). 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

The presence of contaminants, though undesirable in all kind of drug formulations, is really critical in that intent for parenteral administration. Patients who require intensive or prolonged parenteral therapy, the immunocompromised, and neonates and infants might have increased susceptibility to the detrimental effect of contaminants. 

One primary factor that led to the selection of the DS for the SBE-P-CD was the need to economically produce a bulk that is safe for parenteral administration. The safety of the bulk required that it be devoid of any residual P-CD and that the SBE-P-CD exhibit no systemic toxicity. The most economical approach to the elimination of the unreacted P-CD was to derivatize all of the parent CD, a feat accomplished by reaching a DS of approximately 6.5 (SBE7-P-CD). A preliminary evaluation of the potential safety of the SBE7-P-CDs was demonstrated by its minimal involvement in membrane destabilization (20). 

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