Sodium chloride tonicity adjusters

Ophthalmic Dosage Forms. Ophthalmic preparations can be solutions, eg, eye drops, eyewashes, ointments, or aqueous suspensions (30). They must be sterile and any suspended dmg particles must be of a very fine particle size. Solutions must be particle free and isotonic with tears. Thus, the osmotic pressure must equal that of normal saline (0.9% sodium chloride) solution. Hypotonic solutions are adjusted to be isotonic by addition of calculated amounts of tonicity adjusters, eg, sodium chloride, boric acid, or sodium nitrate. 

An increase of the ionic strength of aqueous solutions of glutaminyl and asparaginyl pen-tapeptides has been reported to result in an increased rate of deamidation. Similar results have been noted in an earlier study on cytochrome c, although a lack of effect of ionic strength on stability was observed in a series of pentapeptides Val-Ser-Asn-X-Val and Val-X-Asn-Ser-Val, where X is an amino acid. The ionic strengths of most parenteral formulations of proteins in which sodium chloride is used to adjust the tonicity are sufficiently low that increased deamidation rates resulting from electrolyte addition will not be a major problem. 

Solubility of the drug in the aqueous vehicle, even at 2 percent, was not an issue. Disodium edetate was included to prevent the drug from forming insoluble salts with metal ions such as calcium, zinc and magnesium. The tonicity of the solution was adjusted to within acceptable physiological limits by the addition of sodium chloride. 

Glycerol was used to adjust the tonicity of solution to physiological limits, in preference to sodium chloride, because the latter was shown to reduce the viscosity of carbomer solution to unacceptable levels. The formulation did not include a preservative because it was intended for single-dose application once the pack was opened. 

Parenteral formulations often contain excipients considered to be chemically stable and inert however, all excipients in a formulation may influence the photochemical stability of the product. Dextrose and sodium chloride are used to adjust tonicity in the majority of parenteral formulations. Sodium chloride can affect photochemical processes by influencing solvation of the photoreactive molecules (see Section 14.2.3). The ionic strength is reported to affect the photochemical decomposition rate of minoxidil until a saturation level is reached (Chinnian and Asker, 1996). The photostability of L-ascorbic acid (vitamin C) in aqueous solution is enhanced in the presence of dextrose, probably caused by the scavenging effect of the excipient on hydroxyl radicals mediated by the photolysis of ascorbic acid sucrose, sorbitol, and mannitol have the same effect (Ho et al., 1994). Monosaccharides (dextrose, glucose, maltose, and lactose), disaccharides (sucrose and trehalose), and polyhydric alcohols (inositol, mannitol, and sorbitol) are examples of commonly used lyo-additives in parenterals. These excipients may also affect photochemical stability of the products after reconstitution. 

As high volumes of eye lotions are applied, the product must be isotonic to avoid irritation. However, eye lotions intended to treat ocular oedema should be hypertonic. As discussed under Sect. 10.6.1 the tonicity of eye drops is frequently adjusted with boric acid, borax or a combination thereof. The same is valid for eye lotions. If these excipients are chemically incompatible, or as an alternative, sodium chloride can be used (see Tables 10.11 and 10.12). Suitable excipients adjusting tonicity are summarised in Table 10.9. 

As is the case for the pH level and buffer capacity, adjustment of osmotic value to physiological conditions is advisable. Sodium chloride or glucose are mostly used to adjust tonicity of parenterals. Sometimes deviating medical requirements are to be met. For example, hyperbaric solutions of local anaesthetics are used in spinal anaesthesia (see Sect. 13.2.4). Hyperbaricity in comparison to the cerebrospinal fluid is achieved by a high glucose concentration (7.5 %) which is also a hyperosmolar. 

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