ExAct No.5 RZInformex New Orleans*, USA 19th to 21st April, 2001 PIM (Fair for Pharmaceutical...

No. 5, October 2000

Excipients & Actives for Pharma

Publisher:BASF Aktiengesellschaft

Editorial staff:Dr. Volker Bühler, Valérie Filiatreau,Dr. Hubertus Folttmann, Patrick Glaser,Klaus Kalter, Dr. Karl Kolter, Dr. Siegfried Lang

Concept/Layout:MLW KommunikationsFormGmbH Werbeagentur, Mannheim

Print:Frotscher Druck, Darmstadt

Imprint

Calendar

P h a r m a I n g r e d i e n t s

The

for

SuccessyourChoice

Dear reader,

You may have known ExAct for nearly three years as a customer’snewsletter with its main focus on pharmaceutical excipients.

This year the pharma active ingredients business within the BASFgroup has been reorganized in order to provide you with anintensified and integrated service fulfilling your needs.

BASF now provides a whole range of pharma ingredients fromone source. By focusing on our comprehensive portfolio ofactives, excipients and vitamins and offering a complete technicalapplication and formulation support, we guarantee process safetyas well as freedom in application while enhancing our customers’long-term product and market success.

The ExAct newsletter will continue to provide you with recentfindings, application data and experience relating to our widenedproduct range for the pharmaceutical industry.

Yours sincerely,

BASF AktiengesellschaftMarketingPharma Ingredients

Gabriel Tanbourgi

30th January to 2nd February, 2001InformexNew Orleans* , USA

19th to 21st April, 2001PIM (Fair for Pharmaceutical Ingredients)Kuala Lumpur, Malaysia

11th to 13th June, 2001INTERPHEX Asia (Internat. Exposition for the Pharmaceutical Industry)Singapur, Singapore

23rd to 27th June, 200128th International Symposium on Controlled Release of Bioactive MaterialsSan Diego* , USA

10th to 12th July, 2001CPhI, Pharmaceutical Ingredients ChinaShanghai, China

3rd to 5th October, 2001CPhI, Pharmaceutical Ingredients WorldwideLondon*, United Kingdom

21st to 25th October, 2001AAPS (American Association of Pharmaceutical Scientists) Annual MeetingDenver*, USA

9th to 12th November, 2001PHARMA INDIA (Internat. Congress andExposition for the Pharmaceutical Industry)Mumbai, India

* BASF will be represented.

Riboflavin 100 page 2–3 KollicoatY SR 30 D page 4–5 KollidonY VA 64 page 6–7One Source:The Portfolio page 8–11

Preview page 12 News page 12New Media page 12

0.1 1.0 10.0 100.0 1000.0

Particle Diameter [µm]

Volume [%]

20

10

0

20

10

0

0.1 1.0 10.0 100.0 1000.0

Particle Diameter [µm]

Volume [%]

IntroductionIn general, direct-compressible actives have gainedmore and more importance. Expensive and timeconsuming granulation steps are avoided – if possible– and replaced by direct compression. Therefore thedemand for direct-compressible substances increasedwithin the last years. This is especially the case forsubstances which are difficult to handle in their purecrystalline form like Riboflavin. Crystalline Riboflavinshows poor flowability and bad dissolution properties.Therefore BASF invested in new technology toproduce an improved direct-compressible productspecially designed for the food/pharma requests.

Direct-compressible Riboflavin formulations generallyconsist of granules with a certain amount of excipientsto provide binding and disintegration properties. BASFoffers a direct-compressible 100% grade whichcombines the advantages of improved powder prop-erties and optimized release rates with the highestpossible potency: Riboflavin 100.

ManufactureRiboflavin 100 is manufactured by a natural fermenta-tion process using a non-GMO microorganism,Ashbaya gossypii. Since the soy products utilized forthe fermentation are also not genetically modified weare able to supply our customer with a GMO-freeproduct. The fermentation process guarantees aproduct of highest quality and purity.

Technical advantages of Riboflavin 100

Outstanding product properties: homogeneous particle size good flowability high purity reduced dusting good compressibility excellent dissolution

Particle formMany of the disadvantages in handling syntheticRiboflavin result from its particle form (2). Particles inform of needles show poor flow properties (6) and lowbulk density (4). Especially the production of highpotency Riboflavin tablets becomes difficult or evenimpossible. BASF’s Riboflavin 100 however consistsof round particles (1) with a smooth surface leadingto a higher bulk density (3).

FlowabilityDue to the round particle form and its slightly coarserparticle size (7, 8), Riboflavin 100 has an improvedflowability compared to the synthetic material (5).

Moreover it shows better results in the electrostaticcharging test. These two factors determine the superiorhandling and processing properties of Riboflavin 100.

PurityHPLC tests prove that beside its excellent physicalproperties Riboflavin 100 shows also outstandingquality regarding purity of the material. Whereassynthetic Riboflavin includes several by-products (10),BASF’s Riboflavin 100 has less additional peaks withremarkable lower quantity (9).

Food fortificationIn addition to its excellent handling properties, Ribo-flavin 100 shows good mixing behavior with reducedtendency to subsequent segregation. A typical examplein food fortification is the flour test. A flour mixture con-taining three percent of Riboflavin is mixed thoroughlyand sieved. The less flour mixture remains upon sieve250 µm the better the mixture. As can be seen inpicture (11), BASF’s Riboflavin 100 has considerablybetter mixing and sieving properties. These resultscan also be expected in the fortification of other foodproducts like instant powders. The fortification of softdrinks or other liquids in the range of typical pH valueswith Riboflavin 100 results in the same color as withsynthetic Riboflavin.

Microscope photograph of Riboflavin 100 (1) andsynthetic Riboflavin (2); magnification: x126.

Bulk density of Riboflavin 100 (3) [0.35 g/ml] andsynthetic Riboflavin (4) [0.12–0.18 g/ml].

Particle size distribution of Riboflavin 100. (7)

Flowability of Riboflavin 100 (5) and syntheticRiboflavin. (6)

Riboflavin 100Vitamin B2 in a new shape.U. Sindel

BASF ExAct page 2 – No. 5, October 2000

Tabletting propertiesIdentical coloration compared to synthetic Riboflavin isalso achieved for the use of Riboflavin 100 in pharmaapplications like tablets. Good flowability and homo-geneous particle size distribution result in excellenttabletting properties. Even formulations containing 50mg and more of Riboflavin per tablet are easily com-pressible and show excellent dissolution. The dissolu-tion in water has been improved compared to synthetic

Particle size distribution of synthetic Riboflavin. (8)

1 2

5 6

3 4

rele

ased

rat

e [%

]

0 30 60 90 120 150 180 210 240 270 300 330 360

minutes

100

80

60

40

20

0

100

80

60

40

20

0

5 10 15 20 25 min

mAU

Table 1: Composition per tablet

Riboflavin 100Kollidon CLLudipressAvicel PH 102Magnesium stearateAerosoil 200

Tablet mass

50 mg9 mg

160 mg80 mg2 mg6 mg

307 mg

page 3 – No. 5, October 2000 BASF ExAct

Flour test with Riboflavin 100 in comparison withsynthetic Riboflavin. (11)

100

80

60

40

20

0

5 10 15 20 25 min

mAU

HPLC chromatogramof Riboflavin 100. (9)

HPLC chromatogramof synthetic Riboflavin100. (10)

Dissolution profileof tablets containing50 mg of Riboflavin100. (12)

Riboflavin 100Vitamin B2

loss: 1–4%

SyntheticRiboflavin

Vitamin B2loss: 20–40%

upon sieve250 µm

through sieve50 µm

Riboflavin. This gives benefits in applications wherea high performance dissolution is required.

A tablet containing 50 mg of Riboflavin 100 wasmanufactured at a low compression force of 4 kNresulting in about 70 N hardness without any friability.

DissolutionThe USP requirement for the dissolution of tabletscontaining Riboflavin is 75% within 45 min. Figure(12) shows the dissolution profile of high-potencyRiboflavin 100 tablets. The release rate of 75% evenafter 30 minutes indicates clearly a high reliabilityregarding dissolution speed in tablet formulations.

ConclusionsRiboflavin 100 has demonstrated to be aproduct of high quality with good handling properties for food as well as pharma applica-tions. Therefore it should be the product ofchoice for difficult formulations where excellent powder properties are required.


rele

ased

dru

g [

%]

0 4 8 12 16 20 24

time [h]

◆ 10% Propylene glycol ▲ 10% Triethyl citrate ■ 5% Triethyl citrate● 5% Triacetin ▲ 5% Acetyl tributyl citrate

80

70

60

50

40

30

20

10

0

rele

ased

dru

g [

%]

0 4 8 12 16 20 24

time [h]

100

90

80

70

60

50

40

30

20

10

0

● 0% Talc ■ 25% Talc ▲ 50% Talc ◆ 75% Talc

Coating level 3mg/cm2


Table 1: Composition andpreparation of the pellets

IngredientCaffeine powderAvicel PH 101Granulac 230Kollidon VA 64

Total

(%)1043.7543.75 2.5

100

Table 2: Composition and preparationof the spray suspension

Inlet air temperatureOutlet air temperatureAtomizing pressureSpraying rateDryingCoating levelSpraying timeSolids content ofthe spray suspension

60°C35°C1.0 bar11.5 g/min40°C/3 min3 mg/cm2

about 35 min

20%

Dissolution of caffeinepellets coated withKollicoat SR 30 D anddifferent plasticizerswithout furtheradditives.(Figure 1)

Influence of talc on therelease rate of caffeinepellets.(Figure 2)

was first added to the given amount of water. ThenKollidon SR 30 D was stirred in. The pigment disper-sion was homogenized using a corundum mill andadded slowly to the polymer dispersion while stirring.

IntroductionControlled release film coatings generally do notconsist only of the controlled release polymer but alsocontain various excipients such as plasticizers,coloring agents, antitack additives, pore formers orsuspension stabilizers. These additives have differingdegrees of influence on a variety of film properties, thedissolution rate and the film coating process. KollicoatSR 30 D is a new polyvinyl acetate based polymerdispersion for the manufacture of controlled releasecoated dosage forms [1]. While the influence ofplasticizers on the mechanical film properties hasalready been described [2], no data are yet availableconcerning the other excipients.

PurposeThis study was performed to determine the influenceof additives commonly used in coating formulationson the coating process and film properties. Thisknowledge can be used to optimize coating formula-tions and to improve and expedite their development.

Materials and MethodsMaterialsKollicoat SR 30 D is a polyvinyl acetate dispersionstabilized with polyvinylpyrrolidone and sodium laurylsulfate (BASF AG); caffeine (Knoll AG), Pharsil(dimethicone, Wacker); Aerosil 200 (Degussa),Granulac 230 (lactose, Meggle).

All ingredients were blended in a Diosna-mixer for 5minutes, moistened with water until a readily mould-able mass was obtained (approx. 48% water). Themass was then mixed thoroughly for another 3 minutesextruded in an Alexanderwerk apparatus with a vertical1.5 mm sieve and the resulting granules were trans-ferred to a spheronizer (Heller) and rounded for 10minutes. The still moist pellets were dried in a fluidizedbed granulator and then sieved to obtain the requiredparticle size (0.7–1.4 mm).

The recommended addition rate of 1,2 Propylene gly-col is 10% referred to the dry polymer. Propylene glycol

KollicoatY SR 30 DInfluence of additives on the properties of films and coated dosage forms.K. Kolter, T. Rock

Polymer dispersionParts byweight (g)

Compo-sition (%)

47.0 (14.1)

1.436.6

3.5 0.5 0.510.5

100

190.00(57.00) 5.66147.97

14.15 2.02 2.02 42.45

404.30

Kollicoat SR 30 D(dry polymer)1,2 Propylene glycolWater

Pigment dispersionTalcTitanium dioxideSicovitY Red 30Water

Total

Table 3: Coating processThe coating was applied on 0.5 kg caffeinepellets in a fluidized bed coater (AeromaticStrea 1) under the following conditions:

No. 5, October 2000 BASF ExAct

rele

ased

dru

g [

%]

0 4 8 12 16 20 24

time [h]

100

90

80

70

60

50

40

30

20

10

0

■ 5% glycerol monostearate ▲ 50% glycerol monostearate● 25% dimethicone ◆ 50% dimethicone ◆ without additive

rele

ased

dru

g [

%]

0 4 8 12 16 20 24

time [h]

100

90

80

70

60

50

40

30

20

10

0

■ 25% Aerosil ▲ 25% Magnesium stearate ● 50% Magnesium stearate▲ 25% Tricalcium phosphate ● 50% Tricalcium phosphate ◆ 10% Aerosil

rele

ased

dru

g [

%]

0 4 8 12 16 20 24

time [h]

90

80

70

60

50

40

30

20

10

0

▲ 10% Propylene glycol (uncured) ▲ 10% Propylene glycol (cured 24h/60 °C)● 5% Triethyl citrate (uncured) ● 5% Triethyl citrate (cured 24h/60 °C) ◆ 10% Propylene glycol+ pigments (uncured) ◆ 10% Propylene glycol + pigments (cured 24h/60 °C)■ 5% Triethyl citrate + pigments (uncured) ■ 5% Triethyl citrate + pigments (cured 24h/60 °C)




Influence of finelydispersed additiveson drug release ofcaffeine pellets.(Figure 3)

Influence of glycerolmonostearate anddimethicone on drugrelease of caffeinepellets.(Figure 4)

Curing effect ofcaffeine pellets withand without additives.(Figure 5)

DissolutionDissolution tester (Pharmatest PTW-S), medium:890 ml 0.08M HCl (0–2 h) and phosphate bufferpH 6.8 (2–24 h), paddle with 50 rpm.

Results and DiscussionThe use of different plasticizers resulted in very similardissolution rates (Figure 1). No differences wereapparent between propylene glycol 10% and triethylcitrate (5% and 10%), while triacetin (5%) and ATBC(5%) produced slightly slower dissolution rates.

The excipient talc – widely used in coating preparations– accelerated dissolution with increasing concentration(Figure 2) at constant coating level. It should benoted, however, that especially at very high talc con-centrations the polymer content was much lower andwas no longer sufficient to completely bind the solids.

Very fine particulate solids like Aerosil 200, magne-sium stearate or tricalcium phosphate in higher con-centrations interfere greatly with film formation, sincedissolution occurs very rapidly (Figure 3).Lipophilic antitack additives like glycerol monostearateor dimethicone slow down dissolution in the lowerconcentration range and accelerate it at higherconcentrations (Figure 4).

The additives had no impact on the curing behavior ofthe pellets. Even after high thermal stress (24 h/60 °C)dissolution was almost unchanged. Coating formula-tions with several additives also showed the samebehavior (Figure 5).

Conclusions The type of plasticizer used has almost no

influence on dissolution. Antitack additives in low to medium concentra-

tions also hardly affect dissolution. Fine particulate solids markedly accelerate

dissolution, especially at higher concentrations.

References[1] Technical Information KollicoatY SR 30 DJune 1999, BASF AG.[2] K. Kolter and F. RuchatzProceedings AAPS Congress New Orleans, November 1999, 4225.


Ratio: 6 : 4

Kollidon 30Kollidon VA 64MC PH 101HPMC 2910Maltodextrin DE 18

[°]

2835414244

[s]

7,5blockblockblockblock

MeanParticle Size

D [4,3]

BulkDensity

HausnerRatio

FlowabilityFlow timeTable 2 Angle of

Repose

PurposeDry binders are intended to improve tablet formationby direct compression with the main emphasis onimproving the mechanical properties [1], i. e. thehardness and friability of the tablets. Apart from mi-crocrystalline cellulose and the cellulose ethers,polyvinylpyrrolidone is probably the best-known drybinder. An almost unknown dry binder is Kollidon VA64 (copovidone), a vinylpyrrolidone vinyl acetate-copolymer (Figure 1)[2].

(Figure 1)

The objective of this study was to investigate theeffectiveness of different dry binders and to correlate itwith physicochemical properties.

Experimental MethodsMaterialsDry Binder: Kollidon 30 (povidone), Kollidon VA 64(copovidone) (BASF AG); Avicel PH 101 (microcrystal-line cellulose (FMC); Pharmacoat 606 (hydroxypropyl-methylcellulose 2910) (Shin Etsu); Maldex 18 (malto-dextrin) (Amylum).

IngredientsDi-Tab (Rhône-Poulenc); ascorbic acid powder,Ludipress, Kollidon CL (BASF AG); magnesiumstearate (Bärlocher); Aerosil 200 (Degussa).

MethodsThe dry binders were tested in several formulations(Table 1). A dicalcium phosphate tablet (A), withexcipients which are not soluble in water and a vitaminC tablet (B), with water-soluble constituents. To obtaindetailed information on their compression properties,the pure dry binders were compressed (C).

Powder properties■ bulk and tap density (Erweka volumeter)■ angle of repose (Pfrengle funnel)■ particle size (Malvern Mastersizer)

TabletingThe ingredients (Table 1) were passed through an800-µm sieve and blended for 10 min in a Turbulamixer. The tablets (A) and (B) with a weight of 500 mgwere produced on a Korsch PH 106 rotary press (30

rpm, 12 mm, beveled edge) and (C) with a weightof 500 mg on a Korsch EK0 single punch press(30 tablets/min, 12 mm, beveled edge) with variedcompression forces (10, 18, 25 kN).

Tablet propertiesHardness, weight and dimensions were determinedusing a Kraemer tablet tester (HT-TMB).

Results and DiscussionThe dry binders tested exhibited considerabledifferences in their powder properties (Table 2)which are of interest with reference to tabletability.

The particle size determinations clearly show thatKollidon VA 64 is the finest product and should, withits shell like structure (Figure 2), be able to coat drugand filler particles and bind them together under com-pression.

The hardness of the tablets (A) made with Kollidon VA64 places them in a class of their own (Figure 3).

At a compression force of 18 kN and a dry bindercontent of 50 mg, the hardness of the tablets exceedsthat of tablets without a dry binder by 120%. If the samecompression force is used in each case and the dry

binder content is increased from 25 to 50 to 75 mg,Kollidon VA 64 gives the steepest increase in hardness.

Vitamin C powder (B) was selected as a substancethat is very difficult to compress into tablets and inmix-tures with excipients, also greatly reducescompressibility. The compression force-hardnesscurves (Figure 4) are similar in appearance to thosefor the tablets of formulation A:

without dry binder: low hardnesswith HPMC 2910,Kollidon 30 andMC PH 101: slight improvementswith Kollidon VA 64: exceptional hardness

Because of the polymerized vinyl acetate component,Kollidon VA 64 is a softer and more plastic materialthan the other dry binders. This is confirmed by thelow glass transition temperature (103°C).

The plasticity values of the products (Figure 5) weredetermined from the force-displacement curves (C).Kollidon VA 64 possesses a high plasticity of over90% that remains constant from 10 to 18 to 25 kN.

KollidonY VA 64An excellent dry binder.D. Flick, K. Kolter

CH3

C

H––––––CH–CH2–––––––CH–CH2––––––H

N O O

n m

O

Di-TabAscorbic AcidLudipressDry BinderKollidon CLAerosil 200Magnesium Stearate

Total

Table 1Formulations

(A)%

90, 85, 80––

5, 10, 154.5–

0.5

100.0

–40.0

51.3, 46.3, 41.35, 10, 15

3.00.240.5

100.0

–––

99.5––

0.5

100.0

(C)%

(B)%

1,241,371,401,371,34

[ m]

5043658274

[g/ml]

0,3890,2410,3260,3670,522


▲ Kollidon VA 64 ▲ Kollidon 30 ◆ HPMC 2910■ MC PH 101 ● without dry binder ● Maldex 18

140

120

100

80

60

40

20

0

hard

ness

[N

]

5 10 15 20 25 30compression force [kN]

■ 10 kN ■ 18 kN ■ 25 kN

100

80

60

40

20

0

Pla

stic

ity

in [

%]

Kollidon 30 Kollidon MC PH 101 HPMC 2910 Maldex 18 VA 64

without Kollidon 30 Kollidon MC PH 101 HPMC 2910 Maldex 18dry binder VA 64

100

80

60

40

20

0

Compression Force: 18 kN■ without dry binder ■ 25 mg dry binder■ 50 mg dry binder ■ 75 mg dry binder

hard

ness

[N

]

Hardness ofDicalcium Phoshatetablets withincreasing amountsof dry binders.(Figure 3)

Compression force –hardness profile ofVitamin C tablets.(Figure 4)

Plasticity ofdry binder.(Figure 5)

Scanning electron micros-copy Kollidon VA 64.

(Figure 2)

Conclusions Kollidon VA 64 possesses unique properties as

a dry binder, irrespective of the formulation,which far exceed those of all other materials tested.

Important information can be derived on the effectiveness of dry binders from force displace-ment curves.

The dry binding properties of a substance canbe attributed to various physical properties likeparticle shape and plasticity.

References[1] Lieberman, Lachman and Schwartz, Pharmaceutical Dosage Forms, Marcel Dekker (1998).[2] V. Bühler, Kollidon – Polyvinylpyrrolidone forthe pharmaceutical industry, BASF AG (1996).

50 mg dry binder


One SourceBASF – worldwide ingredient source for the pharma industry.

determine their quality. BASF products are manu-factured to the modern standards of quality manage-ment in the pharmaceutical industry, i. e. ISO standardsand Good Manufacturing Practice (GMP). Each batchis analyzed and issued with a Certificate of Analysisthat confirms its pharmacopoeia quality or specifica-tion requirements.

Our production facilities meet the requirements ofnational and international authorities. Highly motivatedstaff permanently contributes to the improvement ofthe quality standards and the reliability of BASFproducts.

BASF is one of the world’s leading chemical com-panies. Profound know-how in chemistry includingpolymer chemistry have yielded in a wide range ofhigh-quality bulk active ingredients, excipients andvitamins. With proven brands like Kollidon BASF haswritten history in pharmaceutical technology. For 60years BASF has been a reliable source of pharmaceu-tical ingredients and a partner for the pharmaceuticalindustry all over the world.

Pharmaceutical ingredients, like finished pharma-ceutical products are subject to strict quality require-ments. A variety of chemical and physical parameters

PortfolioBrochure Actives Excipients Vitamins

Analgesics

Ibuprofenanalgesic, anti-inflammatory

Purines

CaffeineCNS stimulant, analgesic

Theophyllineanti-inflammatory,bronchospasmolytical

PVP-Iodinedisinfectant with a broadantimicrobial spectrum

Crospovidoneindications: stomach andintestinal disorders

Ephedrines

Ephedrinesympathomimetic

Pseudoephedrinesympathomimetic

Actives

Acetylnorbornene

Amezinium Methyl Sulfateantihypotensive

Bamipine Lactatantihistaminic

Biperidene HCl+ Baseanticholinergic, antiparkinsonian

Carbidopaenzyme inhibitor, antiparkinsonian

Tretinoin/Isotretinoin

actives, mainly prescribedin the acne therapy

Retinolactives for oral and

parenteral applications

Hordenine Sulfate

Hydroxyfenone

Isometheptene-Mucateadrenergic,sympathomimetic

Levopropyl-hexedrine HCladrenergic,sympathomimetic

Mefloquine HClantimalarial

Cathine HClanorexic

Dibenzoyltartaric Acid

Dopamine HCl/Dobutamine HCl sympathomimetic, cardiotonic

Etafedrineadrenergic,sympathomimetic

Hippozympancreasenzyme supplement

Oxymetazoline HCl/ Xylometazoline HClsympathomimetic,vasoconstriction

Phenylpropandione

Pyridylacetonitrile

2-Thienylacetonitrile

Troxerutinedema protective

Verapamilcalcium-antagonist

Assorted Pharma Actives

Paracetamolanalgesic, antipyretic


Quality,Supply safety,Global commitment.BASF – Yourpartner for thefuture.

BASF – Expertise in Health and Nutrition

MLW

Who can resist?KollicoatY MAE 30 DP, andKollicoatY MAE 100 P, ecologi-cally safe and state of the artagents for aqueous coating, are morecost effective and reliably generate higherresistance to gastric fluid than cellulosederivatives. These easy to use coating agentsshorten production processes and are supportedby BASF’s worldwide network of technical expertise.


MLW

Safety for your success: KollidonY. This wide range ofpolyvinylpyrrolidone products reliably ensures your production.Best product quality proves to be successful in a multitude of possible applications and

thus meets – supported by BASF’s worldwide services – the supreme requirements of the pharmaceutical industry.

QualitySupply safetyGlobal commitment.BASF – Yourpartner for thefuture.


a new excipient for smooth directcompression of sustained release dosage forms.


MLW

Sustained relief ! KollidonY SR,

Sustained release!Kollicoat EMM 30 D isa superior quality, totallyaqueous system for the manu-facture of pH-independent controlledrelease membrane coatings and matrixtablets. The cost effective excipient may also be applied

successfully in taste masking and protective coating. For bestresults BASF's technical expertise is always at your service – worldwide.

MLW



MLW

Breakthrough insustained release coating!KollicoatY SR 30 D is a stableaqueous dispersion, characterised by astrong release-retarding activity, a reliable

adjustment of the release rate, easy and costsaving coating processes, excellent film formingproperties, no curing effects, pH-independent releaseprofiles and high storage stability. For best results BASF’stechnical expertise is always at your service – worldwide.



Doxazosin Mesylateantihypertensive

Fluoxetine HClantidepressant

Omeprazoleinhibitior of gastric acid

secretion

Paroxetine HClantidepressant

Selegiline HCland free baseantidepressant,

antiparkinsonian

Sertraline HClantidepressant

Terazosin HClantihypertensive

KollidonY grades

solubilizers, bindersKollidonY 12 PF/17 PFKollidonY 25/30/90 F

disintegrants,suspension stabilizers

KollidonY CLKollidonY CL-M

(dry) binders, film formersKollidonY VA 64

KollicoatY grades

enteric film coatingsKollicoatY MAE 30 DPKollicoatY MAE 100 P

sustained releasefilm coatingsKollicoatY EMM 30 D

New Pharma Actives

Excipients

LudipressY grades

direct compression agentsLudipressY

LudipressY LCE

sustained releasefilm coatingsKollicoatY SR 30 D

sustained release excipientsKollidonY SR

BASF-Service/Support

LabPilot

ValidationDMF Production

R+D Design NDA/ANDA Market Launch


LutrolY grades

act e. g. as binders, film-formers, gelling agents,wetting and dispersing agentsLutrolY E gradesLutrolY F grades

Progress in pharmaceutical forms and the need forefficient manufacturing lead to growing sophisticationof active ingredients and excipients. Multi-disciplinaryR&D teams continuously develop variations onproven products and completely new products tofulfill the customer demands in the future.

Global AvailabilityAs a transnational company BASF is represented allover the world. To take care for the demands of ourcustomers the BASF companies have highly trainedsales teams in place. Various regional distributioncenters enable us to deliver the right product to theright place at the right time. Two production sites forKollidon provides a second-source backup. Withhigh-quality ingredients, a knowledgible technicalservice and a supply safety we aim to maintain aclose partnership with the pharmaceutical industry.

Your Partner for the Future

SolutolY HS 15

non-ionic solubilizer for injection solutions

CremophorY grades

solubilizers and emulsifying agentsCremophorY RH 40

CremophorY ELCremophorY ELP

CremophorY A 6/A 25

Solvents

solvent for veterinaryinjectionsSoluphorY P

solvent for oral, topicaland parenteral drugsPropylene Glycol


MLW


Vitamins

Essential forlife! BASF offersa wide range of highly

pure and easy to handle

and Vitamin premixes as

well as Carotenoids, par-

ticularly developed for therequirements of the pharmaceutical

and nutritional supplement industry.


Tretinoin Isotretinoin Retinol Assorted

Pharma Actives New

Pharma Actives

Excipients KollicoatY

KollidonY LudipressY

LutrolY

CremophorY

SolventsY

SolutolY HS 15

Vitamins

Actives Analgesics Purines Ephedrines PVP-Iodine Crospovidone

BASF now provides a wholerange of pharma

ingredients

Fat-solubleVitamins

Vitamin A (retinol)Vitamin D2 (ergocalciferol)Vitamin D3 (cholecalciferol)

Vitamin E (tocopherol)Vitamin K1 (phytomenadione)

CarotenoidsBeta-carotene

Water-solubleVitamins

Vitamin B1 (thiamine)Vitamin B2 (riboflavin)

NiacinPantothenic acid

Vitamin B6 (pyridoxine)Vitamin B12 (cobalamin)

Vitamin H (d-biotin)Vitamin C (ascorbic acid)

Vitamins

Vitamin C

Preview

page 12 – No. 5, October 2000 BASF ExAct

ME

FMR

1000

1e

Aqueous Enteric Coating ofHumidity Sensitive Drugs.

Aqueous enteric coatings are gaining significantimportance and are substituting organic solventsin manufacturing processes for ecological andeconomical reasons.

It is expected that the large amounts of water inaqueous dispersions are going to interfere with thecore and lead to degradation in the core whenhumidity sensitive drugs, e.g. aspirin or pancreatine,are used. For this reason sometimes subcoatings

In addition to standard tests on Cremophor EL fouradditional specifications on acid-and peroxide value,water contents and limits of alcohol-soluble impuritiesare enclosed.

Since July 2000 a 3rd edition of the CD-ROM con-taining the folder “Generic Drug Formulations” and thebook “Kollidon – Polyvinylpyrrolidone for thepharmaceutical industry” is now available.

In the “Generic Drug Formulations” more than 30 newformulations of different drug forms were included.These formulations mainly are based on our newexcipients like for example the Kollicoat grades, Ludi-press LCE and the research product Kollidon SR.

In the Kollidon book 15 new paper references wereadded to the applications and some parts of theanalytical chapters were actualized (e.g. determina-tion of monomers and formic acid).

Contactare applied when using aqueous coating disper-sions. Among the aqueous enteric coatings, metha-crylic acid copolymer type C (Kollicoat MAE 30 DP)offers advantages in acid resistance and manufac-turing time compared to enteric cellulose derivatives.

ExAct No. 6 will inform you about the suitability ofKollicoat MAE 30 DP for enteric coating of a highlyhumidity sensitive active ingredient (aspirin) withoutusing a subcoating.

For information in advance: Please contact your localBASF company or one of our regional centres.

The United States Pharmacopoeial Conventionpublished a new monograph on “Purified Polyoxyl35 Castor Oil” in volume 26, number 4 of the Pharma-copoeial Forum issued July–August 2000.

Fax: **1/9734265355

Please contact your local BASF companyor one of the following regional centres:

Asia

BASF East Asia RegionalHeadquarters Ltd.Dr. Danilo Mercado7/F., Tower I, South Seas Centre EastTsim Sha TsuiP.O. Box 98427Kowloon, Hong-KongFax: **852/23122261

Europe

BASF AktiengesellschaftLNF/FP – J550Mr. Peter HoffmannD-67056 LudwigshafenGermanyFax: **49/62160-22627

NAFTA

BASF CorporationPharma IngredientsMr. Charles Dods3000 Continental Drive-NorthMount Olive, NJ 07828-1234USA

South America

BASF S.A.Fine ChemicalsMr. Claudio LehmannCaixa Postal 13609701-970 São Bernardo do Campo - SPBrazilFax: **55/117512255

Eastern Europe/Africa/West Asia

BASF AktiengesellschaftLRM/M – D 205Mr. Rolf Hanssen/Mr. Matthias HofD-67056 LudwigshafenGermanyFax: **49/62160-44689

Or visit our website:http://www.basf.de/pharma

NewsCremophor ELP: Monograph on “Purified Polyoxyl35 Castor Oil” published in Pharmacopoeial Forum.

New Media3rd edition of the CD-ROM“Generic Drug Formulation/Kollidon”.

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ExAct No.5 RZInformex New Orleans*, USA 19th to 21st April, 2001 PIM (Fair for Pharmaceutical...

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