Particle size suppositories

The physicochemical properties of the drug molecules and the formulation can also influence rectal drug absorption (Table 7.1). Crucial parameters in this regard include drug concentration, molecular weight, solubility, lipophilicity, pKa, surface properties, and particle size [12]. In addition, formulation properties such as the nature of the suppository base material may play a critical role in regulating drug absorption. 

Softening or melting points and particle size distribution of suspended drug (suppositories). 

Hydrocortisone preparations BP PC All subject to limit on particle size of Hydrocortisone or Hydrocortisone Acetate. See Hydrocortisone Acetate Ointment BP, Hydrocortisone Cream BPC, Hydrocortisone and Neomycin Cream BPC, Hydrocortisone and Neomycin Ear Drops and Eye Drops BPC, Hydrocortisone Eye Ointment BPC, Hydrocortisone Lotion BPC and Hydrocortisone Suppositories BPC... 

As the suppository base is heated before moulding, certain effects can be noted which are unique to this type of medication. Testosterone dissolves when hot in the semisynthetic excipient Witepsol H, to give, on cooling, crystals of about 2-3 /rm in diameter. After dissolution in theobroma oil, the dmg does not crystallise on cooling but remains dissolved as a solid solution. In the former case, high absorption rates are obtained, while in the latter poor absorption is achieved. Because of the effect of particle size on the viscosity of suspensions (see section 7.4.4) it is preferable to avoid the incorporation of ultra-fine crystals as the resultant melt of suspension has a higher viscosity than those produced from coarser crystals. 

When a restraining membrane has to be employed, as with suppositories and most semisolids, the retarding properties of the membrane have to be considered and the amount of formulation applied in the test apparatus must be considered before the key parameters, such as particle size of the dmg, are determined. Examples in Fig. 12.9 demonstrate in one test system how the influence of... 

Suppositories should be evaluated for appearance, color, assay, degradation products, particle size, softening range, appearance, dissolution (at 37°C), and microbial limits. 

Sometimes other routes of administration are necessary. Thus, suppositories are used for rectal delivery and sprays for the nasal route. Sublingual delivery can be advantageous, e.g., for nitrate esters. For asthma the use of inhalators has increased considerably as reliable hi-tech delivery systems have been developed. Flere, the uniformity of the inhaled dose (usually a few micrograms), as well as the narrowness of the particle size distribution, must be safeguarded. 

The release of drug from suppository bases is known to be influenced by various factors such as drug-vehicle interactions, vehicle composition, solubility and particle size of drug in vehicle (18). 

Usually the active substance does not dissolve in the base. Even lipophilic substances are often poorly soluble in fatty bases, so most suppositories are suspensions of the active substance in a (solid) vehicle, the suppository base. For these suspension suppositories the particle size of a dispersed active substance is important because it influences ... 

Irritation of the rectal mucosa occurs when large particles are used. A particle size of 180 pm should therefore be the maximum. Irritation of the mucosa may also occur when small particles of an irritating active substance dissolve (too) quickly. This happens for instance when acetylsalicylic acid with a particle size of 45 pm is used in suppositories. It has a fast release of the active substance from the suppository and it dissolves rapidly, but as a result it irritates the mucosa. Therefore acetylsalicylic acid should be used with a particle size of 180 pm. 

In the preparation of suspension suppositories it is important that the used particles of the active substance are small and remain small (don t reagglomerate). Small particles being essential for a correct content and a sufficient content uniformity of the suppositories, dispersion of the active substance in the suppository base will usually be preceded by or combined with particle size reduction, see Sects. 29.2 and 29.3). Large primary particles should be ground and agglomerates should be broken up. If an active substance is not available in the required particle size, the coarse powder must be ground in a rough stone or porcelain mortar. Active substances kept in stock in the required primary particle size... 

For enemas with an oily vehicle, the considerations regarding solubility of active substance and choice of particle size resemble those for fatty suppositories (see Sect. 11.4.1). The process of release and absorption of the active substance is also largely comparable to that of fatty suppositories just the melting step is not necessary. 

In the preparation of Paracetamol-codeine suppositories FNA (Table 11.5), paracetamol (45) is used as small particles because they provide a faster release rate [25]. In addition, the small particles sediment less rapidly during the preparation of the suppositories. Particles with this degree of fineness, however, establish a poor flow and have a high bulk volume. This makes them unsuitable for processing into capsules. For this purpose the paracetamol quality (90-500) is used. For sieve ranges in relation to particle size see Table 23.3. 

Drug delivery methods include oral administration, transdermal absorption, injection (subcutaneous, intravenous, and intramuscular), sprays, insert (suppositories) implantation (subcutaneous, brain, bone), patches (oral or nasal, mucosa, and dentin) [13]. When gels are used for DDS, the shape and size considered will depend on the method of administration. For example, gel particles must be less than several hundred nm for injection. For this purpose, microcapsules, nanocapsules, microgels, coacervates, and microspheres are used. 

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