Oral solids active substances

Uses Pharmaceutical excipient, film-former for enteric coating of solid oral dosage forms, esp. for controlled release of drugs masks unpleasant tastes and odors barrier between incompat. active substances moisture barrier protecting against atmospheric humidity Features Effective barrier to gastric juice protects acid-sensitive drugs releases active at site of action... 

Solid oral dosage forms are dosage forms that are usually swallowed to release the active substance at one or more sites of the digestive tract mainly for a systemic effect [1]. Solid dosage forms can be a powder or a mixture of powders, often further processed into tablets or hard capsules. The latter are the most common dosage forms delivered to patients [2]. 

Most industrially manufactured herbal medicinal products are oral dosage forms. Liquid preparations (fluid extracts, tinctures) have advantages as to dose flexibility but an unacceptable taste can be a problem in clinical practice. The latter can be circumvented by using solid oral dosage forms containing a dry extract of the herbal medicine. Tablets and capsules with pulverized herbal active substances are also available commercially. Some herbal medicines have to be taken as loose powders. A tea can be prepared from pulverized herbal medicines, either l(X)se or in teabags, or from an instant herbal tea [4, 5]. 

Oral powders are preparations consisting of solid, loose, dry particles of varying degrees of fineness. They contain one or more active substances, with or without excipients and, if necessary, colouring matter (...) and flavouring substances. They are generally administered in or with water or another suitable liquid. They are presented as single-dose or multidose preparations [6]. 

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. 

Solid oral dosage forms are preferably prepared with the active substance as such. The particle size of active substances in fast-release preparations should preferably be not larger than 180 pm to reach a compromise between dissolution rate and flowability. If the raw material consists of particles that are too large, the particles should be reduced in size (see Sect. 29.2). 

Solid oral divided dosage forms are prepared by dividing a mixture of the active substance and excipients evenly over a dosing mould, so every unit corresponds to one dose. In the case of capsules or oral powders, the powder is spread over the capsule shells or powder papers, respectively. Moulds should be filled evenly. Therefore, good flowability is required. 

Solid oral dosage forms can be modified in various ways to alter the release profile of the active substance. Preparations with such an altered release profile are called modified-release preparations. Some of the reasons have been presented previously (Sect. 4.9.1). 

Many active substances are sensitive to light, and therefore, oral solid dosage forms have to be packaged in a light-protecting container. This is especially relevant to capsules with a transparent shell. Powders are packaged in a carton... 

Active substances that are dissolved in water are, if they remain in solution, immediately available for absorption after taking on an empty stomach. If they precipitate in the acidic environment of the empty stomach the precipitation will often be so fine that it easily passes the closed pylorus and re-dissolves, after which rapid absorption is still possible. The pharmaceutical availability (actually the dissolution rate of the solid substance) of suspensions for oral use depends on many factors including solubility in vivo, the crystal modification and the particle size and the viscosity of the suspension. In practice it occurs that an active substance (such as phenobarbital) may be formulated as a suspension in water or as a solution in a lipophilic solvent such as acetem (see Sect. 23.3.6). Beware that changing from a suspension into a solution may cause a great increase in absorption rate and thus cause a change in pharmacodynamics. 

The main choice will be between an oral solution and an oral suspension. For some active substances an emulsion or solubilisate is the appropriate form. However in some cases (e.g. because of an intermediate solubility of the active substance) the pharmacist will have no other option than to dispense an oral solid dosage form and instruct the patient how to manipulate it safely (see Sect. 37.6.2). Proper consideration of the options may prevent formulation mistakes with probably severe consequences. This especially applies to the unreflected use of suspending bases for rendering an oral solid into an oral liquid. 

Oral solutions can be physically unstable through crystallizing of dissolved solids, which in practice may occur when solutions are put in the fridge. The solubility of most active substances is lower at low temperature than at higher temperatures (see also Sect. 18.1). And if they are dissolved in a concentration that is just below their solubility... 

If the active substance is not available as raw material it may be processed from oral solid dosage forms by adapting those. Not all solid dosage forms however are tit for such an operation. Tablets with a gastro-resistant coating or modified-release tablets should not be crushed unless the product information confirms its suitability, see further Sect. 4.10.7. 

Lozenges and pastilles are solid, single-dose preparations intended to be sucked to obtain a local effect in the oral cavity and the throat. They contain one or more active substances, usually in a flavoured and sweetened base. They are intended to dissolve or disintegrate slowly in the mouth when sucked. They have to comply with most of the requirements for tablets. Lozenges are hard preparatirais, pastilles are soft. 

There are numerous examples of medicinal products in which dissolution rate enhancing technologies are applied to increase the bioavailabiUty or absorption rate of an active substance. Cardiac glycosides should be given as micronised particles in a solid oral dosage form because otherwise their dissolution rate and hence their bioavaUability is too low. Piroxicam was shown to be absorbed faster when given as a cyclodextrin complex, which increases the dissolution rate. Similarly, the bioavailabiUty of albendazole as a cyclodextrin complex was increased compared to crystalline non-complexed albendazole, based on the same mechanism. And finally, the bioavailabiUty of amorphous chloramphenicol is higher than that of crystalline chloramphenicol. 

In addition to the active ingredients, solid oral dosage forms will also contain a range of substances called excipients. The role of excipients is essential in ensuring that the manufacturing process is successful and that the quality of the resultant formulation can be guaranteed. The appropriate selection of excipients and their relative concentrations in the formulation is critical in development of a successful product. 

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