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International Journal of Pharmaceutics 231 (2002) 8395

Enteric coated HPMC capsules designed to achieveintestinal targeting

Ewart T. Cole a,*, Robert A. Scott a, Alyson L. Connor b, Ian R. Wilding b,Hans-U. Petereit c, Carsten Schminke c, Thomas Beckert c, Dominique Cade a

a Capsugel Diision of Pfizer Inc., Fabrikmattenweg 2, CH-4144 Arlesheim, Basel, Switzerlandb Pharmaceutical Profiles Ltd, Mere Way, Ruddington Fields, Ruddington, Nottingham NG11 6JS, UK

c Roehm GmbH & Co. KG, Kirschenallee, DE-64293 Darmstadt, Germany

Received 4 June 2001; received in revised form 20 August 2001; accepted 29 August 2001

Abstract

The enteric coating of HPMC capsules containing paracetamol was investigated. Two enteric polymers, Eudragit

L 30 D-55 and Eudragit FS 30 D were studied, which are designed to achieve enteric properties and colonic release,respectively. The capsules were coated in an Accela Cota 10, and, as shown by optical microscopy, resulted incapsules with a uniform coating. Scanning electron microscopy of the surface of the capsules illustrate that, incontrast to gelatin, HPMC has a rough surface, which provides for good adhesion to the coating. Dissolution studiesdemonstrated that capsules coated with Eudragit L 30 D-55 were gastro resistant for 2 h at pH 1.2 and capsulescoated with Eudragit FS 30 D were resistant for a further 1 h at pH 6.8. The product visualisation technique ofgamma scintigraphy was used to establish the in vivo disintegration properties of capsules coated with 8 mg cm2

Eudragit L 30 D-55 and 6 mg cm2 Eudragit FS 30 D. For HPMC units coated with Eudragit L 30 D-55,complete disintegration occurred predominately in the small bowel in an average time of 2.4 h post dose. For HPMCcapsules coated with Eudragit FS 30 D, complete disintegration did not occur until the distal small intestine andproximal colon in an average time of 6.9 h post dose. 2002 Elsevier Science B.V. All rights reserved.

Keywords: Hydroxypropylmethylcellulose capsule; Enteric coating; Eudragit; Scintigraphic evaluation

www.elsevier.com/locate/ijpharm

1. Introduction

Enteric coated products are designed to remainintact in the stomach and then to release theactive substance in the upper intestine. The rea-

sons for using enteric coated preparations are welldocumented (Wilding, 2000).

The polymers commonly used to achieve entericproperties are anionic polymethacrylates (copoly-merisate of methacrylic acid and either methyl-methacrylate or ethyl acrylate (Eudragit),cellulose based polymers, e.g. cellulose acetatephthalate (Aquateric) or polyvinyl derivatives,e.g. polyvinyl acetate phthalate (Coateric).

* Corresponding author. Tel.:+41-61-705-5111; fax: +41-61-705-5118.

E-mail address: [email protected] (E.T. Cole).

0378-5173/02/$ - see front matter 2002 Elsevier Science B.V. All rights reserved.

PII: S0378 -5173 (01 )00871 -7

E.T. Cole et al. / International Journal of Pharmaceutics 231 (2002) 839584

Colon targeting products are also designed toremain intact in the stomach but in additionintended to release the active substance furtheralong the gastrointestinal (GI) tract, e.g. at theileocaecal junction or in the colon (Ashford andFell, 1994). The site specific delivery of drugs tothe colon has implications in a number of thera-peutic areas (Leopold, 1999).

As previously mentioned, site specific deliveryinto the upper intestine has been achieved formany years by the use of pH-sensitive coatings(Healey, 1989). By applying a thicker coatingand/or raising the threshold pH at which dissolu-tion of the coating begins, colon specific deliveryusing enteric polymers has been achieved (Hardyet al., 1987a). Tablets containing mesalazine andcoated with Eudragit S 100, which dissolvesabove pH 7, are marketed in a number of coun-tries (Asacol, GlaxoSmithKline, UK) (Dew etal., 1983). Mesalazine tablets coated with Eu-dragit L100, which dissolves above pH 6, arealso commercially available (Claversal and Salo-falk) (Hardy et al., 1987b).

The majority of the enteric and colon deliverysystems are based on coated tablets or pelletswhich are filled into conventional hard gelatincapsules. However, during the early stages of drugdevelopment some new chemical entities (NCEs)present a challenge in testing for efficacy due toinstability in gastric fluids or because of irritationin the GI tract. The limited amount of drugsubstance available during the early stage oftenprecludes the development of a coated pellet ortablet formulation. Since the coating process isindependent of the capsule contents, there areclear advantages resulting from the ability to coata capsule. Thus, the oral pharmacological and/ortherapeutic efficacy of the NCE can be deter-mined without resorting to extensive formulationdevelopment studies which are expensive, timeconsuming and, in many instances, impossible atthis point in the development of the NCE. Addi-tionally, the capsule provides the possibility todeliver liquid or semi-solid formulations to thesmall or large intestine.

The most commonly used material for manu-facturing capsules is gelatin. Although it is possi-ble to coat hard gelatin capsules (Murthy et al.,

1986; Thoma and Bechtold, 1992) the process is atbest very sensitive, especially if an aqueous coat-ing system is used, and can lead to shell embrittle-ment and poor adhesion of the coat to the smoothgelatin surface. A pre-coating can reduce interac-tions between the gelatin and the enteric polymerbut is time consuming and complicated.

A colonic drug delivery system, based on astarch injection moulded capsule, has been de-scribed (Watts, 1995). This system has all theadvantages of a capsule described above but suf-fers from the disadvantage of requiring a speciallydesigned capsule filling and sealing machine, thusnarrowing the field of application of thetechnology.

HPMC capsules have been available commer-cially, mainly to the dietary supplement industryas a vegetarian alternative to gelatin, for approxi-mately 10 years (Ogura et al., 1998). As HPMC isoften used as a pre-coating material for entericcoated tablets, it may be expected that the appli-cation of enteric type polymers to a capsule madefrom HPMC would result in good polymer topolymer adhesion and compatibility.

Gamma scintigraphy is an elegant imagingtechnique which allows the intestinal performanceof pharmaceutical formulations to be visualized(Wilding et al., 2001; Nick, 1996). Over the last 20years, the approach has become the technique ofchoice for probing the complex interaction ofdrug preparations/formulations with the heteroge-neous environment of the human gut (Wildingand Newman, 1998).

In this paper, we describe the manufacture oftwo different Eudragit coated HPMC capsulesand their in vitro/in vivo performance.

2. Materials and methods

2.1. Coating materials

Two commercially available aqueous methacry-late coating dispersions (Roehm GmbH, Darm-stadt, Germany) were used in this study.Eudragit L 30 D-55 (Methacrylic Acid Copoly-mer Dispersion, NF), designed to achieve entericproperties, is a copolymer of methacrylic acid and

E.T. Cole et al. / International Journal of Pharmaceutics 231 (2002) 8395 85

ethyl acrylate and dissolves at a pH of 5.5. Eu-dragit FS 30 D is a 30% dispersion of a copoly-mer of methacrylic acid, methyl acrylate andmethylmethacrylate. Due to the free carboxylicacid group the polymer dissolves at pH 7 orabove making it particularly suitable for deliveryinto the colon (Gupta et al., 2001).

Excipients used for the coating dispersions weretriethyl citrate, NF (Morflex Inc., Greensboro,NC, USA) as a plasticizer, Polysorbate 80 (Tween80 V, ICI Espana, SA, Barcelona, Spain) as anemulsifier and Mono and Di Glycerides, NF(Imwitor 900, Huls AG, Witten Germany) as aglidant. The composition of the coating disper-sions and their method of preparation are given inTable 1.

In order to increase the flexibility and the adhe-sion of the enteric coating from methacrylic acidcopolymer dispersion, the amount of plasticizerwas adjusted to 20%, based on the polymer. Talcwas not added as an anti sticking agent so as toavoid any discoloration of the capsule surface.Due to the lower glass transition temperature ofthe polymer in Eudragit FS 30 D, a glidant wasneeded to reduce the tackiness. Thus 8%, calcu-

lated on the polymer, of Mono and Di Glycerides(glyceryl monostearate) was added, using polysor-bate 80 as a co-emulsifier. Furthermore, in con-trast to talc, GMS does not increase thebrittleness of coatings due to its physico chemicalproperties. The solid concentration of the sprayliquids was adjusted to 15%, in order to achieve asuniform a coating as possible.

2.2. Capsule filling and coating

Size 0 capsules (Capsugel Division of Pfizer Inc)of surface area 5.0 cm2, made from hydrox-ypropyl methylcellulose without colouring agent,were filled by hand with 380 mg paracetamol(Rhodia France) into which had been mixed 10mg natural abundance samarium oxide. The cap-sules were sealed with the LEMS process (Cole,2000) using a modified sealing fluid.

Capsule coating was carried out in an AccelaCota 10 (BWI Manesty) with a batch size of 5 kg.For each trial the pan was loaded with 4.936 kgsize 1 HPMC capsules filled with 250 mg of aparacetamol formulation and 130 size 0 capsules.This size difference enabled the capsules contain-

Table 1Composition and preparation of the coating dispersions used to coat HPMC capsules

Enteric coating Colonic coating (Eudragit FS 30 D)(Eudragit L 30 D-55)

Eudragit Dispersion 2287.5 g=686.2 g polymer 2287.5 g=686.2 g polymerTriethyl citrate 34.3 g137.2 gGlyceryl 54.9 g

Monostearate65.9 gTween 80 (33%

aqueous solution)3065.2 gWater 2873.5 g5489.9 g=823.5 g total 5316.1 g=797.4 g total solidssolids

Dispersion preparationTEC added to water and Tween 80 added to water and heated to 63 C with stirringhomogenised

GMS added and stirred for 10 min. and resulting suspensions allowedAdded to Eudragit underto cool to below 40 CstirringTEC addedAdded to Eudragit under stirring


Table 2Operating parameters used to coat HPMC capsules with Eu-dragit L 30 D-55 and Eudragit FS 30 D

ValueParameter

Spray gun BWI Manesty1 mmNozzle diameter12 rpmSpeed of rotation1.3 barAtomising pressure9 m3 min1Inlet air volume35 CInlet air temperature2530 COutlet air temperature

Temperature of capsule bed 2527 CSpray rate 4.2 g min1 kg1 per

capsulesSpraying time 263 minDrying conditions 5 min at 30 C

testing in 0.05 M phosphate buffer of pH 6.8. Thecolonic capsules were tested for 2 h at pH 1.2,followed by 1 h at pH 6.8 and finally in phosphatebuffer of pH 7.4. Paracetamol concentrationswere determined by UV spectrophotometry at awavelength of 300 nm.

2.4. Scanning electron microscopy (SEM)

To characterise the surface properties ofHPMC capsules the SEM (Jeol JSM 35) tech-nique was used. As a comparison, the surface of agelatin capsule was also examined. In an attemptto characterise the interface between HPMC andthe coat a coated capsule was cleaved. The samplewas prepared as a mechanically cleaved cross-section.

2.5. Optical microscopy

Low Resolution optical microscopy (NikonLabophot 2A) was used to document the unifor-mity of film thickness on the domed area of anHPMC capsule and also on the junction wherethe cap and body meet. The capsule cross-sectionwas prepared by encapsulating the whole capsulein a slow-setting resin which was allowed to setfor 24 h. The sample was then cut with a diamondsaw and ground and polished to achieve the de-sired longitudinal cross-section.

2.6. In io ealuation

The product visualisation technique of gammascintigraphy was used to establish the in vivodisintegration properties of the coated HPMCcapsules in a group of eight healthy volunteers.The objectives of the scintigraphic evaluationwere to establish both the intestinal site and timeof initial/complete capsule disintegration follow-ing fasted dosing.

This was a two way randomized crossoverstudy in eight healthy male or non-pregnant fe-male volunteers. All subjects received either theEudragit L 30 D-55 or Eudragit FS 30 Dcoated HPMC capsules in randomized order afteran overnight fast. The Clinical Protocol for thestudy was approved by the Quorn Research Re-

ing samarium oxide to be sampled from the bulkcapsules. At various time intervals, during capsulecoating, samples were taken corresponding to atheoretical coating thickness of 6, 8 and 10 mgcm2. At the end of the coating process thecapsules had received 12 mg cm2 of polymersubstance. The operating parameters used duringthe coating process are provided in Table 2. Asthe mechanical properties of hydrophilic polymersare influenced by the residual moisture, any dry-ing by pre-heating or high process temperaturesmust be avoided. Due to the low minimum film-forming temperatures of the coating dispersions,the temperature of the capsules could be keptbetween 25 and 27 C during spraying. By usingsuch mild process conditions any drying of thecapsule shells or spray drying of the atomised mistcan be avoided. After the coating process thecapsules were dried on trays for 2 h at 30 C.

2.3. In itro dissolution studies

To select the appropriate coating thickness forthe capsules to be evaluated in the in vivo scinti-graphic studies dissolution testing on the size 0capsules was undertaken using USP Apparatus 2at 50 rpm, in 900 ml of medium at 37 C with awire sinker. Due to the small number of capsulesavailable only limited in vitro testing was possible.

For the enteric capsules 2 h of exposure in 0.1N hydrochloric acid (pH 1.2) was followed by


view Committee and all volunteers provided writ-ten Informed Consent to participate in the study.

Neutron activation methods can be used toradiolabel dosage forms for scintigraphic studies.These techniques require the addition of a stablenon-radioactive isotope within a formulation;subsequent irradiation in a neutron source con-verts the isotope into a gamma emitting radionu-clide (Digenis and Sandefer, 1991; Kenyon et al.,1995). In order to validate this technique, theirradiation process must be shown to have nosignificant effect on the formulation, i.e. thepreparation must behave in a similar manner bothprior to and following the irradiation procedure.Coated capsules were irradiated for 4.5 min in aneutron flux of 1012 n cm2 s1. In vitro dissolu-tion tests showed that the neutron activation pro-cess did not adversely affect the performance ofthe dosage form.

The volunteers arrived at the study site havingfasted from midnight. Anterior anatomical mark-ers containing 0.1 MBq 99mTc were taped to theskin, where the mid-clavicular line meets the rightcostal margin so that they lay in approximatelythe same transverse plane as the pylorus. Eachsubject received a single preparation radiolabelledwith 1 MBq 153Sm on each of two occasions. Thepreparations were administered at approximately08.00. Subjects remained fasted until 4 h post-dose at which time a standard lunch was pro-vided. An evening meal was also provided at 9 hpost-dose.

Anterior scintigraphic images were recorded atfrequent intervals for 12 h post-dose, using agamma camera (General Electric Maxicamera)with a 40 cm field of view and fitted with a lowenergy parallel hole collimator. Images wererecorded at approximately 10 min intervals until 8h post-dose and at approximately 20 min intervalsuntil 12 h post-dose. The times provided for thetransit and disintegration properties of the twoenteric coated formulations are the mid-point val-ues of the two images either side of the intestinalevent. Return visits were made to the clinical unitat 24 h post-dose to allow the acquisition of afurther scintigraphic image. Acquired images wereinitially of 50 s duration. The volunteers remainedmoderately active throughout the study period

and all images were acquired with the subjectsstanding in front of the gamma camera.

3. Results and discussion

3.1. Microscopy of uncoated and coated capsules

Coatings on gelatin capsules often suffer frominsufficient adhesion between the shell and thecoating. Thus previous workers in the area ofenteric coating have found it necessary to pre-coatgelatin capsules with, for instance, a cellulosederivative, either to promote adhesion of poly-mers to the capsule shell (Murthy et al., 1986) orto improve gastro-resistance (Plaizier-Vercammenet al., 1992). A procedure recommended for coat-ing gelatin capsules (Roehm Technical Brochure,1994) also involved pre-coating with Eudragit L30 D-55 plasticized with glycerol to improve adhe-sion and storage stability. When the capsule itselfis made of a cellulose derivative it would beexpected, based on the experience with entericcoating of tablets with a pre-coating of HPMC,that a pre-coating step could be eliminated.

Gelatin capsules have a very glossy surface dueto the fact that the amount of regular reflectionfrom the surface is high and the amount of diffusereflection is low. In contrast, HPMC capsuleshave a visually matt surface with a greateramount of diffuse reflection, suggesting a moreirregular surface. SEMs of the surface of HPMCand gelatin capsules are shown in Fig. 1 wherethis difference is clearly visible. During the coat-ing process the temperature of the capsule bedreaches 2527 C. At this temperature HPMC issoluble and will start to dissolve in the aqueousbased film providing a strongly adhesive surface.Gelatin, on the other hand, is only slightly solubleat this temperature and its surface characteristicswill remain virtually unchanged. Fig. 2 shows aSEM of the cross-section of a cleaved surfacethrough a capsule coated with 10 mg cm2 Eu-dragit FS 30 D. The contours of the coatingmaterial are seen to follow the irregular surface ofthe HPMC capsule. During the cleaving process itwas observed that the strength of the interfacewas superior to that of either the substrate or the


coating material. It is suggested that the highstrength of the bond between HPMC and the filmis a combination of the irregular surface and thetackiness of the partially dissolved surface.

In contrast to tablets, capsules are of muchlower density, which could result in capsules stick-ing together to give a non-uniform coating. Fig. 3shows a cross-section through a domed end of an

Fig. 1. Scanning electron micrographs of the surface of HPMC and gelatin capsules.


Fig. 2. Scanning electron micrograph of the cross-section of a cleaved surface through an HPMC capsule coated with 10 mg cm2

Eudragit FS 30 D.

HPMC capsule coated with 10 mg cm2 Eudragit

L 30 D-55 and a longitudinal cross-section of acapsule coated with 6 mg cm2 Eudragit L 30D-55. These micrographs confirm that a uniformcoating thickness around the curved surface of thecapsule as well as along the flat surface wasachieved. No pores or cracks can be observed, dueto the well controlled coating process. In addition,the critical area of overlap between the cap andbody of the capsule is covered with polymer ensur-ing gastric integrity.

During the coating process no significant loss ofcoating material was observed as was demonstratedby good agreement between the actual and theoret-ical weight of the coated capsules. This is confirma-tion of the excellent compatibility between theHPMC capsule and the anionic methacrylate dis-persions.

3.2. In itro dissolution

The dissolution profiles from the capsules coatedwith Eudragit L 30 D-55 and Eudragit FS 30 Dare shown in Fig. 4. No paracetamol was released

over 2 h at pH 1.2 from the capsules coated with6 and 8 mg cm2 Eudragit L 30 D-55. At pH 6.8release of paracetamol was rapid, with very littledifference between the two coating thicknesses. Inorder to ensure in vivo gastric integrity, the cap-sules coated with 8 mg cm2 Eudragit L 30 D-55were selected for evaluation in the scintigraphicstudy.

No release of paracetamol was detected at pH 1.2over 2 h or at pH 6.8 over the subsequent 1-h periodfor the capsules coated with Eudragit FS 30 D. AtpH 7.4 the capsules coated with 6, 8 and 10 mgcm2 all opened rapidly and release of paracetamolcommenced. Incomplete release of paracetamolwas due to the inclusion of drug by pockets ofpolymer which did not dissolve under the gentleconditions of the dissolution test. It was consideredthat the minimum coating to achieve a 3 h in vitrolag time (2 h at 1.2 and 1 h at 6.8) would be suitableto achieve in vivo capsule opening either in theterminal ileum or colon; therefore, the capsuleformulation coated with 6 mg cm2 of Eudragit

FS 30 D was selected for in vivo evaluation.


Tablets coated with a monolayer of entericpolymer will show small amounts of drug release,usually around 12% per h, when tested at a pH

below that of the solubility of the polymer due todiffusion through the film. At these pH values norelease of paracetamol was detected from either

Fig. 3. Optical micrographs of HPMC capsules coated with Eudragit L 30 D-55. (Top) Cross-section of domed end of capsulecoated with 10 mg cm2 Eudragit L30 D-55. (Bottom) Longitudinal cross-section through a capsule coated with 6 mg cm2

Eudragit L30 D-55.


Fig. 4. Dissolution of paracetamol from HPMC capsules coated with Eudragit L 30 D-55 and Eudragit FS 30 D. N=3.

capsule system demonstrating that the HPMCcapsule provides a system of low permeability anda good barrier to drug diffusion at the pH, whereprotection is required.

As can be seen from Fig. 4 variation in coatinglevels had little influence on the dissolution profi-les of paracetamol confirming the robustness ofthe formulation and the good compatibility be-tween HPMC and the polymethacrylate films.

3.3. Human product isualisation

Time-lapse photography of intestinal perfor-mance was assessed by obtaining scintigraphicimages at frequent intervals for approximately 12h post-dose. Analysis of the images provided de-tailed information on the GI transit and in vivodisintegration of the Eudragit L 30 D-55 (Table3) and Eudragit FS 30 D (Table 4) coatedcapsules.

The major factor influencing the gastric emp-tying of oral dosage forms is whether they are

administered with or without food. In the fastedstate, stomach residence time is predominantlycontrolled by the frequency of the phase IIIhousekeeper wave, which occurs approximatelyevery 2 h. Therefore, not surprisingly, gastricemptying of the capsules occurred within this timeinterval for the majority of subjects.

Both capsule types remained intact in the stom-ach which confirmed the gastro-resistant proper-ties of the Eudragit L 30 D-55 and Eudragit FS30 D polymers. In addition, the interaction of thepolymer and underlying capsule substrate wasstrong in vivo, providing excellent evidence ofenteric protection for the coated units.

Following gastric emptying, the site and time ofdisintegration were strongly correlated with thechoice of Eudragit polymer. For the HPMCunits coated with Eudragit L 30 D-55, completedisintegration occurred in the small bowel (Fig. 5)in all but one subject confirming that once gastricemptying has occurred, the capsule disintegratesrelatively rapidly within the small intestine.


In contrast, the HPMC capsules coated withthe relatively new polymer, Eudragit FS 30 D,were more resistant to in vivo dissolution withcomplete disintegration occurring lower downthe GI tract in the mid to distal small intestineand proximal colon (Fig. 6). Enteric coatingsthat dissolve at relatively high pH values havebeen used previously to target drug delivery tothe colon (Watts and Illum, 1997).

A number of researchers have concluded thata change in luminal pH cannot be used reliably

and routinely as a mechanism to deliver drugsspecifically to the colon (Ashford and Fell,1994). However, the data from this studydemonstrate that in seven of the eight subjectsdosed with the FS 30 D coated units, initial andcomplete capsule disintegration occurred be-tween the mid to distal small intestine and prox-imal colon suggesting that the subjects intestinalpH was sufficient to dissolve the coating on thisformulation and thereby provide for distal intes-tinal targeting.

Table 3Transit and disintegration of the Eudragit L 30 D-55 coated HPMC capsules (h)

Gastric emptying Colon arrival Initial disintegration Complete disintegrationSubject

Time Site Time Site

MSB3.2PSB2.81 2.00.2 1.4 MSB 1.9 MSB20.4 1.53 MSB 1.9 MSB

PSB1.3PSB1.34 0.90.8 2.6 1.95 DSB 3.2 AC

2.5 PSB6 3.60.1 DSB 1.3 PSB0.4 1.67 MSB

1.58 2.0 DSB 2.5 DSBMean 2.41.80.8

0.7 0.6S.D. 0.988n 8

PSB, proximal small bowel; MSB, mid small bowel; DSB, distal small bowel; AC, ascending colon.

Table 4Transit and disintegration of the Eudragit FS 30 D coated HPMC capsules (h)

Colon arrival Initial disintegrationSubject Complete disintegrationGastric emptying

TimeSiteTime Site

2.51 2.7 5.0PSB MSB0.5 3.62 MSB 5.6 DSB

3 AC10.0DSB3.54.02.37.0DSB3.8 AC4.10.64

0.7 2.6 3.0 AC 6.5 AC52.86 3.70.3 AC 4.7 HF-7 4.32.5 MSB/DSB 6.0 DSB

AC10.0AC9.08 4.02.9Mean 3.51.5 4.2 6.9

0.81.1S.D. 2.12.0885n 8

PSB, proximal small bowel; MSB, mid small bowel; DSB, distal small bowel; AC, ascending colon; HF, hepatic flexure.


Fig. 5. Time lapse drug delivery from the Eudragit L 30 D-55 HPMC capsules in subject 7.

4. Conclusion

The investigations described demonstrate thatthe enteric coating of HPMC capsules is an indus-trially viable process. The matt surface of thecapsule provides a good substrate for adhesion ofthe coating material, which results in an all round

uniform film, providing gastric integrity. Scinti-graphic techniques demonstrated that in the case ofEudragit L 30 D-55, disintegration of the capsulewas relatively rapid within the small intestine. Thecapsules coated with Eudragit FS 30 D, however,disintegrated lower down the GI tract towards thedistal small intestine and proximal colon.


Enteric coated HPMC capsules can thus beconsidered to provide a good container for drugsduring the early development phase providing thepossibility of drug release either in the small intes-tine or towards the colon.

Acknowledgements

The authors gratefully acknowledge contribu-tions from Dr Rod Smith and Jim Scott at P.A.Consulting Group, Melbourn, Herts, UK, for

Fig. 6. Time lapse drug delivery from the Eudragit FS 30 D HPMC capsules in subject 7.


providing the SEMs and OMs and for helpfuldiscussions in interpreting the pictures, Dr Nico-las Madit, Dr Xionwei He and ElizabethGroshens from Capsugel R&D Laboratories, Col-mar, France, for support in testing of HPMCcapsules and finally, Wolfgang Weisbrod ofRoehm for his valuable contribution to the coat-ing formulation concept.

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