Coating with non-ionic polymers

Basic actives such as sodium salicylate may interact with CAP and create a micro pH greater than 5.5. A suitable subcoat layer was then required <65>. The subcoat or isolating layer was usually used to separate the core material from the enteric coating polymers. This layer should hinder or reduce the effect from the core, as pH values, to the enteric layer.

Thoma and Kräutle <187> have used HPMC as a barrier coat prior to the enteric coating consisting of aqueous dispersion of coating agent HPMCP or CAP. TEC was used as a plasticizer. The result showed that the swelling of CAP enteric coated tablets can be reduced, whereas the HPMCP coated pellets were not influenced by this subcoat. The subcoat from an aqueous system of HPMC was often used, though the effect from the subcoat on the stability of the enteric dosage form was not well studied.

The following polymers were generally used as subcoats because of non-ionic property and the authors have investigated their effect on the dosage form.

1.1.6.1 Hydroxypropyl methylcellulose (HPMC)

HPMC was used by many researchers, for example: as a film forming agent

<10,97,89,106>, a matrix for producing tablets <13,196> or for layering of drug <149>.

The use of HPMC was reviewed in the literature <1,162>. The physical properties of

free films from HPMC such as crystallinity, Tg, intrinsic viscosity were investigated

<71,107,95>.

Mc Philips, Craig, Royall and Hill <95> have shown that the glass transition temperature (Tg) of HPMC powder measured by modulated temperature differential scanning calorimetry (MTDSC) was about 162 °C and the Tg of HPMC films was about 164 °C – 167 °C. Lehtola et al. <88> studied the Tg of free films prepared from aqueous based HPMC plasticized with different types of polyethylene glycol (PEG 400, 1500 and 4000).

By using the DSC technique they have found that the Tg of free film from HPMC alone was 119 °C. The Tg of HPMC with PEG 400 was between 119 - 138 °C depending on the concentration of PEG which was varied from 10 to 30 % w/w. If the concentration of PEG was increased then the Tg was reduced. The Tg of HPMC plasticized with PEG was higher than that of HPMC without plasticizer. This may be due to the higher moisture content of unplasticized HPMC film. The Tg of HPMC and PEG 1500 or PEG 4000 surprisingly kept almost constant at 130 and 136 °C, respectively though the concentration of PEGs was varied from 10 to 30 % w/w. The free film from HPMC plasticized with 20 % w/w PEG 400 and 20 % w/w TiO2 showed the Tg of 134 °C which was higher than the Tg of the same film without TiO2. This appearance seems to be due to the hindering of mobility of polymer chains in the presence of pigment particles.

1.1.6.2 Ethyl cellulose (EC)

Physical properties such as crystallinity, Tg or swelling of ethyl cellulose have been reported <167,58,124>. Ethyl cellulose generates very hard or tough films and needs a plasticizer to soften the film, i.e., to improve flexibility and reduce brittleness. The Tg of EC is 120 °C which is defined as the temperature above which EC is in a rubbery state.

Thus an unplasticized EC film would be in the glassy state at temperatures at which products are manufactured and stored and would not perform its intended function. The plasticizer must be able to dissove the polymer to promote chain mobolity and flexibility.

Thus a comparison of the solubility parameters of plasticizers with that of EC is predictive of effectiveness. Alternatively free films can be prepared with various plasticzers at different levels and examined thermomechanically to investigate effectiveness <67>. For example; the softening temperature of Aquacoat ECD and 24 % w/w DBS was reported to be 54 °C. A number of plasticizers were reported to be

compatible with Aquacoat ECD e.g. DEP and DBS because of the value of the solubility parameter <67>.

It is reported that the Tg of Aquacoat ECD is lowered as the concentration of a plasticizer such as DBS, DEP or TEC is increased. This appearance will promote coalescence of polymer particles. The Tg of unplasticized Aquacoat ECD was 129 °C, whereas the Tg of Aquacoat ECD film plasticized with 20 % w/w DBS, DEP or TEC was 44 °C, 44 °C and 36 °C, respectively. The optimum plasticizer level was reported to be 20 – 24 % w/w <179>. Another report showed that the Aquacoat ECD dispersions plasticized with DBS at 15 %, 25 % and 30 % gave intact clear films above 34 °C, 28 °C and 27 °C, respectively. TEC at the same concentrations exhibited a MFFT of 32 °C, 30 °C and less than 23 °C, respectively <117>. The solubility parameter of EC, DEP and DBS was reported to be 21.1, 20.5 and 18.8 (J/m³)^1/2 x 10^–3, respectively.

Therefore, DEP and DBS seemed to be more efficient as a plasticizer for Aquacoat ECD than TEC. Pellets coated with aqueous based systems using Aquacoat ECD were widely studied <118,205,21>. The curing was an important factor for a good coalescence of EC. The combination of EC and other polymers such as HPMC was also studied <59,67,116,117,118,149,179,205>.

1.1.6.3 Polyvinyl alcohol (PVA)

PVA is available in different viscosity grades. It was used as excipient in many fields e.g. production of paper, polymerisation, textile, foils and ceramic <142>. In the pharmaceutical field it can be used as stabilizer in dispersion <85,105>, filler in tabletting <146>, in pelletisation <142>, in microencapsulation <142>, for microparticles

<24,173> or sponges <142> but PVA alone as a film forming agent is not published.

Therefore it is of interest to study the possibility to use PVA for coating of pellets.

The possibility to incorporate PVA instead of gelatine in the sugar coating formulations was studied and the authors mentioned that PVA was a good stabilizer for the sugar coating suspensions <105>. It was also reported that PVA can be used as a stabilizer in the aqueous phase for preparation of microencapsulation using cellulose acetate butyrate <85>. Microspheres of PVA containing diclofenac sodium can be prepared by an emulsion-chemical cross-linking method <33>. The cross-linked PVA was reported to be used for preparing microparticles for the controlled-release oral solid dosage form

<173>. In the tabletting process PVA can be used as a matrix for producing the

compressed tablets containing a water soluble drug <146>. The release- and swelling-behaviour of these tablets were studied.

The possibility of using PVA for the ocular drug delivery was studied in form of liposomes and nanoparticles <24> and the delivery of protein was also studied <68>.

The incorporation of bovine serum albumin into PVA hydrogel films was successfully performed and the effect of the freezing and thawing process and its subsequent release behaviour were reported.

It was reported that PVA can be used to produce the complex containing phenobarbital using spray drying technique <81>. The crystallization of the drug in the polymer PVA shown under a light microscope, by SEM, DSC or X-ray diffraction depended on the concentration of the incorporated drug.

The chemical stability of PVA was studied <2,96>. As PVAs contain residual acetate groups they can therefore be degraded by the hydrolytic process. The elastic behaviour, the internal stress and the swelling of PVA were also studied <174,175>.

The mixture of PVA and HPMC was reported to be used as film forming agents applying PEG 6000 as a plasticizer <160>. The moisture permeation properties of HPMC containing PVA and filled with talc or titanium dioxide have been evaluated using the sorption-desorption technique <119>.