Lactose oral solids

Most adults consume about 25 g of lactose per day (500 mL of milk) without symptoms.When symptoms appear, they are usually mild and dose-related. The dose of lactose in most pharmaceuticals seldom exceeds 2 g per day. It is unlikely that severe gastrointestinal symptoms can be attributed to the lactose in a conventional oral solid-dosage form, especially in adults who have not previously been diagnosed as severely lactose-intolerant. However, anecdotal reports of drug-induced diarrhea due to lactose intolerance have been made following administration of pharmaceutical preparations containing lactose. 

Aldehyde-sugars (glucose) and derived disaccharides of it (lactose) in solid form are, in contrast to the keto-sugars (fructose), incompatible with strongly alkaline compounds and primary amines (ethylenediamine). A brown discolouration (caramellisation) takes place. In the case of primary amines is this called the MaUlard reaction. In mixtures of solid (anhydrous) substances these reactions proceed very slowly and they occur only on the surface of the sugar particle. Thus they may be irrelevant in practice. However, because of this incompatibility the WHO formulation for the oral rehydration salts prescribes anhydrous glucose, which moreover is not combined with sodium bicarbonate but with sodium citrate. It is preferable not to use lactose in capsules with primary aliphatic amines. A more recently reported Maillard reaction is that between lactose and fluoxetine [30]. 

Oral Solid Dosage Forms (OSDF) and Pharma Excipients Market for Polymers (MCC, HPMC, CMC, Ethyl Cellulose, Povidone and Others), Alcohols (Glycerin, Sorbitol, Mannitol, Propylene Glycol), Minerals (Clay, Silicon Dioxide, Titanium Dioxide) and Sugars (Lactose, Sucrose) - Global Industry Analysis, Size, Share, Trends, Analysis, Growth and Forecast, 2012 - 2018,2013. 

Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation, for example, fillers, disintegrants, binders, lubricants and glidants. An added complexity is the fact that certain excipients can have different functional roles in different formulation types. Thus, lactose is widely used as a filler or diluent in solid oral dosage forms, for example, tablets and capsules [2] and as a carrier for inhalation products [3]. 

For the pharmaceutical product development scientist, there is clearly a need for objective information about the practical performance of different excipients and their various grades. In this chapter we set out to bring together the results of some of our ongoing evaluations of the physical and mechanical properties of excipients commonly used for the manufacture of solid oral dosage forms. In this particular article, we have chosen to focus on the fillers that are most commonly used in the manufacture of immediate release tablets microcrystalline cellulose (MCC), lactose, calcium phosphate, and mannitol (1). 

Lactose is widely used in pharmaceutical formulations as a diluent and filler-binder in oral capsule and tablet formulations. It may also be used in intravenous injections. Adverse reactions to lactose are largely due to lactose intolerance, which occurs in individuals with a deficiency of the intestinal enzyme lactase, and is associated with oral ingestion of amounts well over those in solid dosage forms. 

The choice of a diluent may influence the absorption of an active substance, which was seen in the l%Os in Australia. The diluent of phenytoin sodium capsules was changed from calcium sulfate dihydrate to lactose, which strongly enhanced the bioavailabdity of phenytoin sodium. Plasma levels of phenytoin increased up to fourfold, which led to an increased reporting of adverse events [8,9]. This case drew worldwide attention and resulted in an increased awareness of the importance of pharmaceutical availability and bioavailability of active substances in the development of solid oral dosage forms. 

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