Figure 2.4: Structural formula of CAP
Cellulose acetate phthalate (CAP) known as cellulosi acetas phthalus in the Ph.Eur.
1997, cellacefate in the USP XXIV, and cellacephate in the BP 1993. Other synonyms such as cellulose acetate hydrogen 1,2 - benzenedicarboxylate, cellulose acetate monophthalate or cellulose acetylphthalate are mentioned <29>. CAP is a reaction product of phthalic anhydride and a partial acetate ester of cellulose. It contains not less than 21.5 percent and not more than 26 percent of acetyl (C2H3O) groups and not less
C H C
O C OH
CH3
O
O
O O
OR H O CH2OR
H H OR H H
= R n
than 30 percent and not more than 36 percent of phthalyl (o-carboxyl-benzoyl, C8H5O3) groups, calculated on the anhydrous, acid free basis <26>. The limit of phthalyl content stated in EP1997 and BP 1993 however is different from the USP that is 30 - 40 %. The limit of free acid of CAP in USP XXIV, EP 1997 and BP 1993 is the same that means no more than 3 %, whereas the limit in USPXXIII is higher namely not more than 6 %, calculated as free phthalic acid. The free acid was determined by the titration method using dilute methanol as sovent, 0.1 N sodium hydroxide as titrant and phenolphthalein as an indicator <27,28,30>.
CAP is a white, free-flowing powder or colourless flakes, tasteless, odourless or may have a slight odor of acetic acid. It is a hygroscopic substance, practically insoluble in water, alcohols, hydrocarbons and chlorinated hydrocarbons but soluble in dilute solutions of alkalis, a number of ketones, esters, ether alcohols, cyclic ethers and in certain solvent mixtures such as acetone : ethanol, acetone : methanol or ethyl acetate : isopropanol. The relative molecular weight of CAP is ca. 30,000. The glass transition temperature (Tg), melting point (Tm) and minimum film forming temperature (MFFT) of CAP is 160 – 170 °C, 192 °C and 56 °C, respectively <29>. The pKa value of CAP is 4.4 - 4.7 depends on phthalyl content <29>.
There are two commercially available CAP products to be used as a coating dispersion
<7,9>. One is in form of redispersing powder called Aquateric CD, the other one is in form of a ready-to-used dispersion called Aquacoat CPD. Both these two products will be discussed in details in the following part because they will be used in this work.
2.1.6.1 Aquateric CD-910
Aquateric is composed of solid or semi-solid polymer spheres of cellulose actate phthalate ranging in size from 0.05 to 3 µm with average particles of 0.2 µm. Aquateric was accomplished by a special mechanical emulsion technique to produce the submicron size particles and subsequent spray drying after addition of suitable physical barrier materials. In its initial form Aquateric is a dry, white water-insoluble powder. It is then dispersed in water to create the reconstituted latex film coating system. A typical dispersion may consist of 10 - 30 % solids, yet have a viscosity in the 50 - 100 cP range. Aquateric consisted of 70 % CAP, the remainder comprises polyoxypropylene-polyoxyethylene block co-polymer and acetylated monoglycerides for stabilizing the physical property of the product. Diethyl phthalate (DEP) has been found to be an
effective plasticizer for use in Aquateric because of its effective interaction with CAP polymer. It was also reported that propylene glycol showed a good plasticization effect.
Mixed plasticizer systems including DEP, polyethylene glycol (PEG) 400 have been reported to provide fully continuous films for enteric performace as well. PEG 400, on the other hand, tended to over soften the film and resulted in twinning or sticking . In summary the following plasticizers were recommended to be used with Aquateric: the water insoluble plasticizer DEP, the water soluble triacetin, triacetin citrate or propylene glycol and the combination of DEP and triacetin at 1:1 ratio.
Materials used in this work:
The following batches of Aquateric , which was produced by FMC Corporation, Pharmaceutical Division, Philadelphia, USA and distributed by Lehmann & Voss & Co., Hamburg, were used in this work.
Lot. No. L6271, This batch according to the certificate of analysis contained 70 % cellulose acetate phthalate and 2.1 % free phthalic acid.
Lot. No. L9242, This batch as mentioned in the certificate of analysis contained 70 % cellulose acetate phthalate and 1.3 % free phthalic acid.
2.1.6.2 Aquacoat CPD- 30
Aquacoat CPD contained 23 % cellulose acetate phthalate [CAS.No. 9004-38-0], 7 % poloxamer [CAS.No. 9003-11-6] and 70 % water [CAS.No. 7732-18-5]. It is commercially available as a 30 percent by weight dispersion. The typical coating level for enteric coated beads using Aquacoat CPD is 10-15 %. Because of a high surface area of dosage form beads need more coating substances than tablets which need only 6-10 % coating level. Recommended plasticizers for use with Aquacoat CPD include diethyl phthalate (DEP), triethyl citrate (TEC) and triacetin. The amount of 20-24 % plasticizers to Aquacoat CPD latex solids was recommended for the most applications.
For example; if DEP was used at 20 % to solid content of latex, the glass transition temperature (Tg) of Aquacoat CPD was reduced to 34 °C, but using TEC at the same concentration, the Tg was reduced to 35 °C.
Materials used in this work:
The following batches of Aquacoat CPD, which was manufactured by FMC Corporation, Pharmaceutical Division, Philadelphia, USA and distributed by Lehmann & Voss & Co., Hamburg, were used in this work.
Lot No. K9261, This batch as mentioned in the certificate of analysis contained total solid content of 30.2 %. The content of cellulose acetate phthalate was 24 % and of free phthalic acid was 0.4 %. The pH of this dispersion was 2.7 and the viscosity was 12 cP.
Lot No. K0061, This batch as mentioned in the certificate of analysis contained total solid content of 29.5 %. The content of cellulose acetate phthalate was 22 % and of free phthalic acid was 0.5 %. The pH of this dispersion was 2.6 and the viscosity was 13 cP.
Lot No. K9441, This batch as mentioned in the certificate of analysis contained total solid content of 29.6 %. The content of cellulose acetate phthalate was 22 % and of free phthalic acid was 0.5 %. The pH of this dispersion was 2.7 and the viscosity was 12 cP.
Lot No. K9251, This batch as mentioned in the certificate of analysis contained total solid content of 30.2 %. The content of cellulose acetate phthalate was 24 % and of free phthalic acid was 0.7 %. The pH of this dispersion was 2.8 and the viscosity was 12 cP.
2.1.7 Enteric polymer: Hydroxypropyl methylcellulose acetate succinate