Medications excipients

The use of crystalline nanoparticles of cellulose (CNP) allows for paving a new path for the development of nanocosmetics. The CNP for cosmetics application can be produced by hydrolysis of pure cotton cellulose with mineral acids as was described in Section 9.3.1. The paste of CNP for cosmetic application was obtained by evaporation of dilute aqueous dispersion. The powder of CNP was prepared by freeze-drying of the aqueous dispersion. Testing has shown that the obtained powder of CNP meets requirements of the US pharmacopeia 23/NF 18 for inactive medical excipients (Table 9.13). 

If a liquid dosage form of a medication exists, it would seem rational to use this dosage form for administration through a feeding tube. Although such a decision may decrease the potential for tube clogging, it may in some instances decrease tolerability of the medication administration. Sorbitol is an excipient found in many liquid medications in amounts sufficient to cause diarrhea. If diarrhea secondary to sorbitol in a liquid medication is suspected in a patient on EN, contact with the manufacturer to ascertain sorbitol content may be necessary. 

Enbrel is a product now approved for medical use that is based upon this strategy. The product is an engineered hybrid protein consisting of the extracellular domain of the TNF p75 receptor fused directly to the Fc (constant) region of human IgG (see Box 13.2 for a discussion of antibody structure) The product is expressed in a CHO cell line from which it is excreted as a dimeric soluble protein of approximately 150 kDa. After purification and excipient addition (mannitol, sucrose and trometamol), the product is freeze-dried. It is indicated for the treatment of rheumatoid arthritis and is usually administered as a twice-weekly s.c. injection of 25 mg product reconstituted in WFI. Enbrel functions as a competitive inhibitor of TNF, a major pro-inflammatory cytokine. Binding of TNF to Enbrel prevents it from binding to its true cell surface receptors. The antibody Fc component of the hybrid protein confers an extended serum half-life on the product, increasing it by fivefold relative to the soluble TNF receptor portion alone. 

Neorecormon (tradename, also known as epoetin beta) is a recombinant human EPO first approved for medical use in the EU in 1997. It is indicated for the treatment of anaemia associated with various medical conditions, most commonly chronic renal failure and cancer patients receiving chemotherapy. Neorecormon is produced by recombinant DNA technology in a CHO cell line and is manufactured as outlined in Figure 10.5. It is presented in lyophilized format at various strengths (500-10 000 IU/vial) and contains phosphate buffer, sodium chloride, calcium chloride, urea, polysorbate and various amino acids as excipients. 

To demonstrate the ability to evaluate intersample variations, an over-the-counter (OTC) pain relief medication from two different manufacturers was compared. The samples contain three APIs each acetaminophen, aspirin and caffeine. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate 8.1a. Measurements on all samples were collected simultaneously. Tablet A samples from one manufacturer have a reported label concentration of 37%, 37%, and 10%, for the three API components, respectively. Tablet B samples from the second manufacturer contain the same three APIs, at label concentrations of 39%, 39%, and 10 %, respectively. In addition to these samples, tablet C samples are included in the array of tablets. These samples contain only acetaminophen as the API with a reported label concentration of 79%, and are made by the manufacturer who produces tablet A. The remaining mass of all three tablet types represents the excipient (binder, disintegrant, and lubricant) materials. 

The presence or absence of enhancing and/or interfering substances (e.g., inulin-type fructans, fructooligosaccharides, phytates, excipients, medications)... 

Formulation Development. The formulation of the new drug product will be designed in conjunction with medical and marketing input. Excipients to be used will be tested for chemical and physical compatibility with the drug substance. The preliminary formulation design will be optimized at this stage. 

Apte SP, Ugwu SO. A review and classification of emerging excipients in parenteral medications. Pharm Tech 2003 27 46. 

A timely and systematic approach is needed for the independent review of excipients to encourage the development of new excipients. A number of independent review models are used in other industries, such as food, cosmetics, and medical devices, and could be adapted to the review of excipients. IPEC is currently surveying its members to determine which system might be most useful (28), and IPEC has developed an Excipient Master File Guide to standardize and harmonize the information needed to review a new excipient (29). The format of the master file is modeled after the electronic ICH CTD for presenting chemistry, manufacturing, and controls and safety information. 

Transdermal delivery of certain APIs is now common for the treatment of some medical conditions, and there are several excipients that are promoted as transdermal penetration enhancers. One of the earlier materials developed was laurocapram (Azone ). There is a detrimental interaction between laurocapram and mineral oil (liquid paraffin) whereby when both are included in the same formulation, the skin penetration-enhancing properties of laurocapram are lost. Such interactions have implications for extemporaneous mixing of different cream and ointment formulations in the pharmacy. 

PG, similar to glycerin, is a multifunctional excipient that can be an effective preservative when used at concentrations of 15% to 30% in oral solutions. However, formulations containing 35% PG can cause hemolysis in humans. PG exhibits nonlinear pharmacokinetics and when elimination pathways are saturated, serum levels dramatically increase. Pyruvic and lactic acid are produced from the metabolic degradation of PG and can lead to acidosis. Neonates have a longer PG half-life (16.9 hours) compared with adults (5 hours) and seizures, and respiratory depression has occurred in children who have ingested oral liquid medications containing PG (9). Therefore, special consideration should be placed on the amount of PG in formulations that are intended for infants and children. 

H. Suppositories Solid preparations which melt at body temperature delivering medication for at-site treatment or for absorption at that point (usually rectal, vaginal, or urethral). Excipients include cocoa butter, waxy fatty acids, and derivatives, polyethylene glycol, theobroma oil, as well as many ingredients found in G. 

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