Capsules solvent method

Table 4.4 Solvent method developed for some low dose capsules ...

This method is known as solvent method for the preparation of low dose capsules, and is further described in Sect. 4.5.1. The method brings about not only particle size reduction and deagglomeration but is also used for the preparation of triturations of low-dose active substances (see also Sect. 29.1.8). 

For some capsule preparations in pharmacies ordered mixing may be the case. Mixing as the result of the solvent method may be considered as such (Sect. 4.5.1). 

SOP F08-4 1 Capsules with low dosage, preparation by solvent method ... 

Per dosage form list aU applied methods of preparation (such as capsule filling after dry mixing or using the solvent method). 

The standard chemical and biological methods of analysis are those accepted by the JnitedStates Pharmacopeia XXIII as well as the ones accepted by the AO AC in 1995 (81—84). The USP method involves saponification of the sample (dry concentrate, premix, powder, capsule, tablet, or aqueous suspension) with aqueous alcohoHc KOH solvent extraction solvent removal chromatographic separation of vitamin D from extraneous ingredients and colormetric deterrnination with antimony trichloride and comparison with a solution of USP cholecalciferol reference standard. 

The next two chapters concern nanostructured core particles. Chapter 13 provides examples of nano-fabrication of cored colloidal particles and hollow capsules. These systems and the synthetic methods used to prepare them are exceptionally adaptable for applications in physical and biological fields. Chapter 14, discusses reversed micelles from the theoretical viewpoint, as well as their use as nano-hosts for solvents and drugs and as carriers and reactors. 

One of the first methods for making capsules involved polymer coacervation. In this method, macromolecules are dissolved in either the dispersed or continuous phase of an emulsion and are induced to precipitate as a shell around the dispersed phase. Coacervation can be brought about in several ways, such as changes in temperature or pH, addition of salts or a second macromolecular substance, or solvent evaporation (Bungenberg de Jong 1949). 

A second classical method for making capsules from emulsions is to form the shell polymer in situ using interfacial polymerization (Morgan and Kwolek 1959 Wittbecker and Morgan 1959). This method is similar to the nylon rope trick often used as a demonstration, where a solution of diacid chloride in organic solvent (such as adipoyl chloride in hexanes) is layered in a beaker with a diamine aqueous phase (such as 1,6-hexadiamine in water Friedli et al. 2005). Because the two monomers meet only at the interface of the two phases, the condensation polymerization to form the polyamide occurs only at the interface. 

Tabiets and capsules Suspensions and solutions Creams and ointments Solvent extraction methods... 

Method. The tablet or capsule containing ephedrine is pulverized and mixed with 70 ml of ethanol at 40 °C for 20 min with magnetic stirring. The resulting solution is filtered and the clear filtrate is diluted to 100 ml. 1 ml of this solution is treated with 5 ml of ethanol, 5 ml of acetone, 1 -2 ml of a solution of DNS-C1 (2 mg/ml in acetone) and 2 ml of a solution of sodium bicarbonate (10 mg/ml in water). The solutions are shaken and placed in the dark for 1 h. An aliquot portion of the resulting mixture is analyzed by TLC on plates of silica gel using benzene-ethanol-acetic acid (90 10 1) as solvent. An alternative procedure for ephedrine has been discussed earlier [123]. 

A better method is to first add an equal volume of dimethylsulfoxide (DMSO) or dimethylformamide (DMF) to the aqueous sample. This breaks both biological and encapsulation membranes and pulls polar and nonpolar material into solution. The second step is to dilute the sample with 10 volumes of water. At this point, nonpolars can be removed by solvent extraction or with a Cig SFE. Charged molecules can be recovered with pH-controlled extraction or with ion pairing reagents. The DMSO or DMF stays with the water layer. Customers have told me they can achieve almost complete recovery of both fat-soluble and water-soluble vitamins from polymer-encapsulated mixtures. Vitamins are encapsulated to protect potency from air-oxidation. Water-soluble vitamins have nonpolar encapsulation fat-soluble vitamins have polar encapsulation. Either vitamin can be extracted by themselves, but they are difficult to extract under the same condition unless DMSO or DMF are used to break both capsules. 

The main mechanism for effecting triggered release is to use pressure to break the shell, and hence release the core contents into the external phase. This is particularly useful when the active material is a high MW molecule (e.g. a protein). The applied pressure can be in the form of simple mechanical pressure (e.g. in carbon paper copying) or high shear conditions. A more subtle method, however, is to use osmotic pressure to break the capsule. This can occur if solvent molecules from the external phase are able to diffuse across the shell into the core. If the core contains molecules (e.g. polymer) which are not able to diffuse across the shell, then clearly there will be an osmotic pressure difference across the shell, which will drive solvent to try to enter the core, leading to possible shell rupture. 

The HPLC method (if a separation of two components is required) should be very simple because it is for the measurement of the API only. However, during the HPLC method there should be no interference at the retention time of the API from any placebo, capsule, or a sample solvent solution. 

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