Pharma Ingredients

The Choice for No. 5, October 2000 your Success Excipients & Actives for Pharma

Dear reader, Riboflavin 100 page 2–3 Y You may have known ExAct for nearly three years as a customer’s Kollicoat SR 30 D page 4–5 newsletter with its main focus on pharmaceutical excipients. Y Kollidon VA 64 page 6–7 This year the pharma active ingredients business within the BASF One Source: group has been reorganized in order to provide you with an page 8–11 intensified and integrated service fulfilling your needs. The Portfolio Preview page 12 BASF now provides a whole range of pharma ingredients from one source. By focusing on our comprehensive portfolio of News page 12 actives, excipients and vitamins and offering a complete technical New Media page 12 application and formulation support, we guarantee process safety as well as freedom in application while enhancing our customers’ long-term product and market success. Calendar The ExAct newsletter will continue to provide you with recent th nd findings, application data and experience relating to our widened 30 January to 2 February, 2001 product range for the pharmaceutical industry. Informex New Orleans*, USA th st 19 to 21 April, 2001 PIM (Fair for Pharmaceutical Ingredients) Kuala Lumpur, Malaysia th th Yours sincerely, 11 to 13 June, 2001 INTERPHEX Asia (Internat. Exposition BASF Aktiengesellschaft for the Pharmaceutical Industry) Marketing Singapur, Singapore Pharma Ingredients rd th 23 to 27 June, 2001 28th International Symposium on Controlled Release of Bioactive Materials San Diego*, USA th th 10 to 12 July, 2001 Gabriel Tanbourgi CPhI, Pharmaceutical Ingredients China Shanghai, China Imprint rd th 3 to 5 October, 2001 CPhI, Pharmaceutical Ingredients Worldwide Publisher: London*, United Kingdom BASF Aktiengesellschaft st th Editorial staff: 21 to 25 October, 2001 Dr. Volker Bühler, Valérie Filiatreau, AAPS (American Association of Pharmaceutical Dr. Hubertus Folttmann, Patrick Glaser, Scientists) Annual Meeting Klaus Kalter, Dr. Karl Kolter, Dr. Siegfried Lang Denver*, USA th th Concept/Layout: 9 to 12 November, 2001 MLW KommunikationsForm PHARMA INDIA (Internat. Congress and GmbH Werbeagentur, Mannheim Exposition for the Pharmaceutical Industry) Mumbai, India Print: Frotscher Druck, Darmstadt * BASF will be represented. BASF ExAct page 2 – No. 5, October 2000

Riboflavin 100

Vitamin B2 in a new shape. U. Sindel

 Introduction In general, direct-compressible actives have gained more and more importance. Expensive and time consuming granulation steps are avoided – if possible – and replaced by direct compression. Therefore the demand for direct-compressible substances increased within the last years. This is especially the case for substances which are difficult to handle in their pure 12 crystalline form like Riboflavin. Crystalline Riboflavin shows poor flowability and bad dissolution properties. Microscope photograph of Riboflavin 100 (1) and Therefore BASF invested in new technology to synthetic Riboflavin (2); magnification: x126. produce an improved direct-compressible product specially designed for the food/pharma requests. Moreover it shows better results in the electrostatic charging test. These two factors determine the superior Direct-compressible Riboflavin formulations generally handling and processing properties of Riboflavin 100. consist of granules with a certain amount of excipients 56 to provide binding and disintegration properties. BASF  Purity offers a direct-compressible 100% grade which HPLC tests prove that beside its excellent physical Flowability of Riboflavin 100 (5) and synthetic combines the advantages of improved powder prop- properties Riboflavin 100 shows also outstanding Riboflavin. (6) erties and optimized release rates with the highest quality regarding purity of the material. Whereas possible potency: Riboflavin 100. synthetic Riboflavin includes several by-products (10), Volume [%] BASF’s Riboflavin 100 has less additional peaks with 20  Manufacture remarkable lower quantity (9). Riboflavin 100 is manufactured by a natural fermenta- tion process using a non-GMO microorganism,  Food fortification 10 Ashbaya gossypii. Since the soy products utilized for In addition to its excellent handling properties, Ribo- the fermentation are also not genetically modified we flavin 100 shows good mixing behavior with reduced are able to supply our customer with a GMO-free tendency to subsequent segregation. A typical example product. The fermentation process guarantees a in food fortification is the flour test. A flour mixture con- 0 product of highest quality and purity. taining three percent of Riboflavin is mixed thoroughly 0.1 1.0 10.0 100.0 1000.0 Particle Diameter [µm] and sieved. The less flour mixture remains upon sieve  Technical advantages of Riboflavin 100 250 µm the better the mixture. As can be seen in Particle size distribution of Riboflavin 100. (7) picture (11), BASF’s Riboflavin 100 has considerably Volume [%] Outstanding product properties: better mixing and sieving properties. These results 20  homogeneous particle size can also be expected in the fortification of other food  good flowability products like instant powders. The fortification of soft  high purity drinks or other liquids in the range of typical pH values

 reduced dusting with Riboflavin 100 results in the same color as with 10  good compressibility synthetic Riboflavin.  excellent dissolution

 Particle form 0 0.1 1.0 10.0 100.0 1000.0 Many of the disadvantages in handling synthetic Particle Diameter [µm] Riboflavin result from its particle form (2). Particles in form of needles show poor flow properties (6) and low Particle size distribution of synthetic Riboflavin. (8) bulk density (4). Especially the production of high potency Riboflavin tablets becomes difficult or even  Tabletting properties impossible. BASF’s Riboflavin 100 however consists Identical coloration compared to synthetic Riboflavin is of round particles (1) with a smooth surface leading also achieved for the use of Riboflavin 100 in pharma to a higher bulk density (3). applications like tablets. Good flowability and homo- geneous particle size distribution result in excellent  Flowability tabletting properties. Even formulations containing 50 34 Due to the round particle form and its slightly coarser mg and more of Riboflavin per tablet are easily com- particle size (7, 8), Riboflavin 100 has an improved Bulk density of Riboflavin 100 (3) [0.35 g/ml] and pressible and show excellent dissolution. The dissolu- flowability compared to the synthetic material (5). synthetic Riboflavin (4) [0.12–0.18 g/ml]. tion in water has been improved compared to synthetic page 3–No.5,October2000 mAU mAU 100 released rate [%] 100 20 20 40 60 80 40 60 80 100 0 0 20 40 60 80 0 06 01010 8 20 4 20 0 30 360 330 300 270 240 210 180 150 120 90 60 30 0 0 5 2 5 min 25 20 15 10 5 0 5 2 5 min 25 20 15 10 5 minutes 100. 50 mgofRiboflavin of tabletscontaining Dissolution profile 100. of syntheticRiboflavin HPLC chromatogram of Riboflavin 100. HPLC chromatogram (12) (10) (9) regarding dissolutionspeedintabletformulations. after 30minutesindicatesclearlyahighreliability even Riboflavin 100tablets.Thereleaserateof75% (12) within45min.Figure containing Riboflavinis75% The USPrequirementforthedissolutionoftablets  resulting inabout70Nhardnesswithoutanyfriability. manufactured atalowcompressionforceof4kN A tabletcontaining50mgofRiboflavin 100 was a highperformancedissolutionisrequired. Riboflavin. Thisgivesbenefitsinapplicationswhere synthetic Riboflavin. Flour testwithRiboflavin 100 incomparisonwith Dissolution  Tablet mass Aerosoil 200 Magnesium stearate Avicel PH 102 Ludipress Kollidon CL Riboflavin 100 Table 1: loss: 20–40% Riboflavin 100

powder properties arerequired. choice fordifficultformulationswhere excellent tions. Thereforeitshouldbethe productof properties forfoodaswellpharma applica- product ofhighqualitywithgood handling Riboflavin 100hasdemonstrated tobea Conclusions showsthedissolutionprofileofhigh-potency loss: 1–4% Vitamin B Vitamin B Riboflavin Synthetic

Composition pertablet 2 2 upon sieve 250 (11) BASF µ m through sieve 50 Ex 307 mg 160 mg µ 50 mg 80 mg m 2 mg 9 mg 6 mg Act BASF ExAct page 4 – No. 5, October 2000

KollicoatY SR 30 D

Influence of additives on the properties of films and coated dosage forms. K. Kolter, T. Rock

 Introduction Table 2: Composition and preparation was first added to the given amount of water. Then Controlled release film coatings generally do not of the spray suspension Kollidon SR 30 D was stirred in. The pigment disper- consist only of the controlled release polymer but also sion was homogenized using a corundum mill and contain various excipients such as plasticizers, added slowly to the polymer dispersion while stirring. Parts by Compo- coloring agents, antitack additives, pore formers or Polymer dispersion suspension stabilizers. These additives have differing weight (g) sition (%) Table 3: Coating process degrees of influence on a variety of film properties, the The coating was applied on 0.5 kg caffeine dissolution rate and the film coating process. Kollicoat pellets in a fluidized bed coater (Aeromatic Kollicoat SR 30 D 190.00 47.0 SR 30 D is a new polyvinyl acetate based polymer Strea 1) under the following conditions: (dry polymer) (57.00) (14.1) dispersion for the manufacture of controlled release 1,2 Propylene glycol 5.66 1.4 coated dosage forms [1]. While the influence of Water 147.97 36.6 Inlet air temperature 60°C plasticizers on the mechanical film properties has Outlet air temperature 35°C already been described [2], no data are yet available Pigment dispersion Atomizing pressure 1.0 bar concerning the other excipients. Talc 14.15 3.5 Spraying rate 11.5 g/min Titanium dioxide 2.02 0.5 Drying 40°C/3 min  Purpose SicovitY Red 30 2.02 0.5 Coating level 3 mg/cm2 This study was performed to determine the influence Water 42.45 10.5 Spraying time about 35 min of additives commonly used in coating formulations Solids content of on the coating process and film properties. This Total 404.30 100 the spray suspension 20% knowledge can be used to optimize coating formula- tions and to improve and expedite their development.

 Materials and Methods 10% Propylene glycol 10% Triethyl citrate ■ 5% Triethyl citrate Materials ● 5% Triacetin 5% Acetyl tributyl citrate Kollicoat SR 30 D is a polyvinyl acetate dispersion 80 stabilized with polyvinylpyrrolidone and sodium lauryl 70 Dissolution of caffeine 2 Coating level 3mg/cm pellets coated with sulfate (BASF AG); caffeine (Knoll AG), Pharsil 60 Kollicoat SR 30 D and (dimethicone, Wacker); Aerosil 200 (Degussa), 50 Granulac 230 (lactose, Meggle). different plasticizers 40 without further Table 1: Composition and 30 additives. released drug [%] preparation of the pellets 20 (Figure 1)

10 Ingredient (%) 0 Caffeine powder 10 04812162024 time [h] Avicel PH 101 43.75 Granulac 230 43.75 Kollidon VA 64 2.5 ● 0% Talc ■ 25% Talc 50% Talc 75% Talc Total 100 100 Influence of talc on the 90 All ingredients were blended in a Diosna-mixer for 5 Coating level 3mg/cm2 release rate of caffeine 80 minutes, moistened with water until a readily mould- pellets. able mass was obtained (approx. 48% water). The 70 (Figure 2) mass was then mixed thoroughly for another 3 minutes 60 extruded in an Alexanderwerk apparatus with a vertical 50

1.5 mm sieve and the resulting granules were trans- 40 ferred to a spheronizer (Heller) and rounded for 10 released drug [%] 30 minutes. The still moist pellets were dried in a fluidized 20 bed granulator and then sieved to obtain the required particle size (0.7–1.4 mm). 10 0 The recommended addition rate of 1,2 Propylene gly- 04812162024 col is 10% referred to the dry polymer. Propylene glycol time [h] page 5 – No. 5, October 2000 BASF ExAct

Dissolution Dissolution tester (Pharmatest PTW-S), medium: 25% Aerosil 25% Magnesium stearate 50% Magnesium stearate 890 ml 0.08M HCl (0–2 h) and phosphate buffer 25% Tricalcium phosphate 50% Tricalcium phosphate 10% Aerosil pH 6.8 (2–24 h), paddle with 50 rpm. 100 Influence of finely 90 dispersed additives  Results and Discussion 80 on drug release of The use of different plasticizers resulted in very similar 70 caffeine pellets. dissolution rates (Figure 1). No differences were (Figure 3) 60 apparent between propylene glycol 10% and triethyl citrate (5% and 10%), while triacetin (5%) and ATBC 50 (5%) produced slightly slower dissolution rates. 40

released drug [%] 30 The excipient talc – widely used in coating preparations 20 – accelerated dissolution with increasing concentration Coating level 3mg/cm2 10 (Figure 2) at constant coating level. It should be noted, however, that especially at very high talc con- 0 04812162024 centrations the polymer content was much lower and time [h] was no longer sufficient to completely bind the solids.

Very fine particulate solids like Aerosil 200, magne- 5% glycerol monostearate 50% glycerol monostearate sium stearate or tricalcium phosphate in higher con- 25% dimethicone 50% dimethicone without additive centrations interfere greatly with film formation, since 100 Influence of glycerol dissolution occurs very rapidly (Figure 3). 90 monostearate and Lipophilic antitack additives like glycerol monostearate 80 dimethicone on drug or dimethicone slow down dissolution in the lower concentration range and accelerate it at higher 70 release of caffeine concentrations (Figure 4). 60 pellets. (Figure 4) 50 The additives had no impact on the curing behavior of 40 the pellets. Even after high thermal stress (24 h/60°C)

released drug [%] 30 dissolution was almost unchanged. Coating formula-

20 tions with several additives also showed the same Coating level 3mg/cm2 behavior (Figure 5). 10

0  Conclusions 04812162024  The type of plasticizer used has almost no time [h] influence on dissolution.  Antitack additives in low to medium concentra- 10% Propylene glycol (uncured) 10% Propylene glycol (cured 24h/60°C) tions also hardly affect dissolution. 5% Triethyl citrate (uncured) 5% Triethyl citrate (cured 24h/60°C) 10% Propylene glycol  Fine particulate solids markedly accelerate + pigments (uncured) 10% Propylene glycol + pigments (cured 24h/60°C) dissolution, especially at higher concentrations. 5% Triethyl citrate + pigments (uncured) 5% Triethyl citrate + pigments (cured 24h/60°C) Curing effect of 90 caffeine pellets with 80 and without additives. Coating level 3mg/cm2 References (Figure 5) 70 [1] Technical Information KollicoatY SR 30 D 60 June 1999, BASF AG. 50 [2] K. Kolter and F. Ruchatz

40 Proceedings AAPS Congress New Orleans, November 1999, 4225. 30 released drug [%] 20

10

0 04812162024 time [h] BASF ExAct page 6 – No. 5, October 2000

KollidonY VA 64

An excellent dry binder. D. Flick, K. Kolter

 Purpose Table 1 (A) (B) (C) Dry binders are intended to improve tablet formation Formulations % % % by direct compression with the main emphasis on improving the mechanical properties [1], i.e. the hardness and friability of the tablets. Apart from mi- Di-Tab 90, 85, 80 – – crocrystalline cellulose and the cellulose ethers, Ascorbic Acid – 40.0 – polyvinylpyrrolidone is probably the best-known dry Ludipress – 51.3, 46.3, 41.3 – binder. An almost unknown dry binder is Kollidon VA Dry Binder 5, 10, 15 5, 10, 15 99.5 64 (copovidone), a vinylpyrrolidone vinyl acetate- Kollidon CL 4.5 3.0 – copolymer (Figure 1)[2]. Aerosil 200 – 0.24 – Magnesium Stearate 0.5 0.5 0.5 (Figure 1) Total 100.0 100.0 100.0

H––––––CH –CH 2–––––––CH –CH 2––––––H N O O O rpm, 12 mm, beveled edge) and (C) with a weight binder content is increased from 25 to 50 to 75 mg, n C m of 500 mg on a Korsch EK0 single punch press Kollidon VA 64 gives the steepest increase in hardness. (30 tablets/min, 12 mm, beveled edge) with varied CH3 Ratio: 6 : 4 compression forces (10, 18, 25 kN). Vitamin C powder (B) was selected as a substance that is very difficult to compress into tablets and in The objective of this study was to investigate the Tablet properties mix-tures with excipients, also greatly reduces effectiveness of different dry binders and to correlate it Hardness, weight and dimensions were determined compressibility. The compression force-hardness with physicochemical properties. using a Kraemer tablet tester (HT-TMB). curves (Figure 4) are similar in appearance to those for the tablets of formulation A:  Experimental Methods  Results and Discussion Materials The dry binders tested exhibited considerable without dry binder: low hardness Dry Binder: Kollidon 30 (povidone), Kollidon VA 64 differences in their powder properties (Table 2) with HPMC 2910, (copovidone) (BASF AG); Avicel PH 101 (microcrystal- which are of interest with reference to tabletability. Kollidon 30 and line cellulose (FMC); Pharmacoat 606 (hydroxypropyl- MC PH 101: slight improvements methylcellulose 2910) (Shin Etsu); Maldex 18 (malto- The particle size determinations clearly show that with Kollidon VA 64: exceptional hardness dextrin) (Amylum). Kollidon VA 64 is the finest product and should, with its shell like structure (Figure 2), be able to coat drug Because of the polymerized vinyl acetate component, Ingredients and filler particles and bind them together under com- Kollidon VA 64 is a softer and more plastic material Di-Tab (Rhône-Poulenc); ascorbic acid powder, pression. than the other dry binders. This is confirmed by the Ludipress, Kollidon CL (BASF AG); magnesium low glass transition temperature (103°C). stearate (Bärlocher); Aerosil 200 (Degussa). The hardness of the tablets (A) made with Kollidon VA 64 places them in a class of their own (Figure 3). The plasticity values of the products (Figure 5) were Methods determined from the force-displacement curves (C). The dry binders were tested in several formulations At a compression force of 18 kN and a dry binder Kollidon VA 64 possesses a high plasticity of over (Table 1). A dicalcium phosphate tablet (A), with content of 50 mg, the hardness of the tablets exceeds 90% that remains constant from 10 to 18 to 25 kN. excipients which are not soluble in water and a vitamin that of tablets without a dry binder by 120%. If the same C tablet (B), with water-soluble constituents. To obtain compression force is used in each case and the dry detailed information on their compression properties, the pure dry binders were compressed (C). Mean Bulk Hausner Flowability Table 2 Particle Size Density Ratio Angle of Flow time D [4,3] Repose Powder properties bulk and tap density (Erweka volumeter) angle of repose (Pfrengle funnel) [ m] [g/ml] [°] [s] particle size (Malvern Mastersizer) Kollidon 30 50 0,389 1,24 28 7, 5 Tableting Kollidon VA 64 43 0,241 1,37 35 block The ingredients (Table 1) were passed through an MC PH 101 65 0,326 1,40 41 block 800-µm sieve and blended for 10 min in a Turbula HPMC 2910 82 0,367 1,37 42 block mixer. The tablets (A) and (B) with a weight of 500 mg Maltodextrin DE 18 74 0,522 1,34 44 block were produced on a Korsch PH 106 rotary press (30 page 7 – No. 5, October 2000 BASF ExAct

Compression Force: 18 kN  Conclusions without dry binder 25 mg dry binder  Kollidon VA 64 possesses unique properties as 50 mg dry binder 75 mg dry binder Hardness of a dry binder, irrespective of the formulation, Dicalcium Phoshate which far exceed those of all other materials tablets with tested. 100 increasing amounts  Important information can be derived on the of dry binders. 80 effectiveness of dry binders from force displace- (Figure 3) ment curves. 60  The dry binding properties of a substance can

hardness [N] 40 be attributed to various physical properties like particle shape and plasticity. 20

0 without Kollidon 30 Kollidon MC PH 101 HPMC 2910 Maldex 18  References dry binder VA 64 [1] Lieberman, Lachman and Schwartz, Pharmaceutical Dosage Forms, Marcel Dekker (1998). [2] V. Bühler, Kollidon – Polyvinylpyrrolidone for Kollidon VA 64 Kollidon 30 HPMC 2910 the pharmaceutical industry, BASF AG (1996). MC PH 101 without dry binder Maldex 18 140 Compression force – 120 hardness profile of Vitamin C tablets. 100 (Figure 4)

80

60 hardness [N]

40

20 Scanning electron micros- 50 mg dry binder copy Kollidon VA 64. 0 (Figure 2)

5 10 15 20 25 30 compression force [kN]

10 kN 18 kN 25 kN Plasticity of dry binder. (Figure 5) 100

80

60

40 Plasticity in [%] 20

0 Kollidon 30 Kollidon MC PH 101 HPMC 2910 Maldex 18 VA 64 BASF ExAct page 8 – No. 5, October 2000

One Source

BASF – worldwide ingredient source for the pharma industry.

Portfolio BASF is one of the world’s leading chemical com- determine their quality. BASF products are manu- panies. Profound know-how in chemistry including factured to the modern standards of quality manage- Brochure polymer chemistry have yielded in a wide range of ment in the pharmaceutical industry, i.e. ISO standards  Actives high-quality bulk active ingredients, excipients and and Good Manufacturing Practice (GMP). Each batch  Excipients vitamins. With proven brands like Kollidon BASF has is analyzed and issued with a Certificate of Analysis  Vitamins written history in pharmaceutical technology. For 60 that confirms its pharmacopoeia quality or specifica- years BASF has been a reliable source of pharmaceu- tion requirements. tical ingredients and a partner for the pharmaceutical industry all over the world. Our production facilities meet the requirements of national and international authorities. Highly motivated Pharmaceutical ingredients, like finished pharma- staff permanently contributes to the improvement of ceutical products are subject to strict quality require- the quality standards and the reliability of BASF ments. A variety of chemical and physical parameters products.

Actives Analgesics Ibuprofen Purines analgesic, anti- Caffeine inflammatory CNS stimulant, analgesic Theophylline Paracetamol anti-inflammatory, analgesic, antipyretic bronchospasmolytical

PVP-Iodine Ephedrines disinfectant with a broad Ephedrine antimicrobial spectrum sympathomimetic Pseudoephedrine Crospovidone sympathomimetic indications: stomach and intestinal disorders Assorted Pharma Actives

 Acetylnorbornene  Cathine HCl  Hordenine Sulfate  Oxymetazoline HCl/ anorexic Xylometazoline HCl  Amezinium  Hydroxyfenone sympathomimetic, Methyl Sulfate  Dibenzoyltartaric  Isometheptene- vasoconstriction antihypotensive Acid Mucate  Phenylpropandione Tretinoin/  Bamipine Lactat  Dopamine HCl/ adrenergic, Isotretinoin antihistaminic Dobutamine HCl sympathomimetic  Pyridylacetonitrile sympathomimetic, actives, mainly prescribed  Biperidene HCl  Levopropyl-  2-Thienylacetonitrile cardiotonic in the acne therapy + Base hexedrine HCl  Troxerutin anticholinergic,  Etafedrine adrenergic, edema protective Retinol antiparkinsonian adrenergic, sympathomimetic sympathomimetic  Verapamil actives for oral and  Carbidopa  Mefloquine HCl calcium-antagonist parenteral applications enzyme inhibitor,  Hippozym antimalarial antiparkinsonian pancreasenzyme supplement page 9 – No. 5, October 2000 BASF ExAct

New Pharma Actives Pilot Lab DMF Production Validation  Doxazosin Mesylate  Selegiline HCl antihypertensive and free base antidepressant, BASF-Service/Support  Fluoxetine HCl antiparkinsonian antidepressant  Sertraline HCl  Omeprazole antidepressant inhibitior of gastric acid secretion  Terazosin HCl antihypertensive R+D Design NDA/ANDA Market Launch  Paroxetine HCl antidepressant

Excipients MLW BASF – Expertise in Health and Nutrition KollicoatY grades

Who can resist? enteric film coatings Y KollicoatY MAE 30 DP, and Kollicoat MAE 30 DP Kollicoat Y MAE 100 P, ecologi- Y cally safe and state of the art Kollicoat MAE 100 P Y MLW Kollidon grades BASF – Expertise in Health and Nutrition agents for aqueous coating, are more cost effective and reliably generate higher resistance to gastric fluid than cellulose derivatives. These easy to use coating agents shorten production processes and are supported by BASF’s worldwide network of technical expertise. solubilizers, binders KollidonY 12 PF/17 PF Y Safety for your success: KollidonY. This wide range of Quality, polyvinylpyrrolidone products reliably ensures your production. Supply safety, Global commitment. Kollidon 25/30/90 F Best product quality proves to be successful in a multitude of possible applications and BASF – Your thus meets – supported by BASF’s worldwide services – the supreme requirements of the pharmaceutical industry.

partner for the MLW future. sustained release BASF – Expertise in Health and Nutrition film coatings disintegrants, Y Kollicoat EMM 30 D suspension stabilizers Y MLW Sustained release! Kollidon CL BASF – Expertise in Health and Nutrition Y Quality Kollicoat EMM 30 D is Supply safety Kollidon CL-M Global commitment. BASF – Your partner for the a superior quality, totally future. aqueous system for the manu- facture of pH-independent controlled release membrane coatings and matrix (dry) binders, film formers Y tablets. The cost effective excipient may also be applied Sustained relief! Kollidon SR, successfully in taste masking and protective coating. For best Y a new excipient for smooth direct results BASF's technical expertise is always at your service – worldwide. Kollidon VA 64 compression of sustained release dosage forms.

Quality Supply safety Global commitment. BASF – Your partner for the future.

MLW sustained release excipients BASF – Expertise in Health and Nutrition KollidonY SR Quality Supply safety Global commitment. BASF – Your partner for the sustained release future. film coatings Breakthrough in KollicoatY SR 30 D sustained release coating! KollicoatY SR 30 D is a stable aqueous dispersion, characterised by a strong release-retarding activity, a reliable adjustment of the release rate, easy and cost saving coating processes, excellent film forming properties, no curing effects, pH-independent release profiles and high storage stability. For best results BASF’s technical expertise is always at your service – worldwide. Y Quality Supply safety Global commitment. BASF – Your Ludipress grades partner for the future.

direct compression agents LudipressY LudipressY LCE BASF ExAct page 10 – No. 5, October 2000

Your Partner for the Future

LutrolY grades  Progress in pharmaceutical forms and the need for efficient manufacturing lead to growing sophistication of active ingredients and excipients. Multi-disciplinary act e.g. as binders, film- R&D teams continuously develop variations on formers, gelling agents, proven products and completely new products to wetting and dispersing agents fulfill the customer demands in the future. LutrolY E grades LutrolY F grades  Global Availability As a transnational company BASF is represented all over the world. To take care for the demands of our customers the BASF companies have highly trained sales teams in place. Various regional distribution centers enable us to deliver the right product to the right place at the right time. Two production sites for Kollidon provides a second-source backup. With high-quality ingredients, a knowledgible technical service and a supply safety we aim to maintain a close partnership with the pharmaceutical industry.

Solvents

solvent for veterinary injections SoluphorY P

solvent for oral, topical and parenteral drugs Propylene Glycol

CremophorY grades

solubilizers and emulsifying agents CremophorY RH 40 CremophorY EL CremophorY ELP Y SolutolY HS 15 Cremophor A 6/A 25

non-ionic solubilizer for injection solutions page 11 – No. 5, October 2000 BASF ExAct

Vitamin C

Vitamins Fat-soluble Vitamins Vitamin A (retinol)

Vitamin D2 (ergocalciferol) Vitamin D3 (cholecalciferol) Vitamin E (tocopherol)

Vitamin K1 (phytomenadione)

W

L M

BASF – Expertise in Health and Nutrition

Carotenoids Essential for life! BASF offers Beta-carotene a wide r ange of highly pure and easy to handle Vitamins Water-soluble and Vitamin premixes as well as Carotenoids, par- ticularly developed for the requirements of the pharmaceutical Vitamins and nutritional s upplement industry. Vitamin B1 (thiamine) Vitamin B2 (riboflavin) Quality Supply safety Global commitment. BASF – Your partner for the Niacin future. Pantothenic acid

Vitamin B6 (pyridoxine) Vitamin B12 (cobalamin) Vitamin H (d-biotin) Vitamin C (ascorbic acid)

BASF now provides a whole Actives Excipients    Y range of pharma Analgesics Tretinoin Kollicoat    Y ingredients Purines Isotretinoin Kollidon  Ephedrines  Retinol  LudipressY  PVP-Iodine  Assorted  LutrolY  Crospovidone Pharma Actives  CremophorY  New  SolventsY Pharma Actives  SolutolY HS 15

Vitamins page 12 – No. 5, October 2000 BASF ExAct

Preview Contact Please contact your local BASF company Aqueous Enteric Coating of are applied when using aqueous coating disper- or one of the following regional centres: Humidity Sensitive Drugs. sions. Among the aqueous enteric coatings, metha- crylic acid copolymer type C (Kollicoat MAE 30 DP) Aqueous enteric coatings are gaining significant offers advantages in acid resistance and manufac- Asia importance and are substituting organic solvents turing time compared to enteric cellulose derivatives. BASF East Asia Regional in manufacturing processes for ecological and Headquarters Ltd. economical reasons. ExAct No. 6 will inform you about the suitability of Dr. Danilo Mercado Kollicoat MAE 30 DP for enteric coating of a highly 7/F., Tower I, South Seas Centre East It is expected that the large amounts of water in humidity sensitive active ingredient (aspirin) without Tsim Sha Tsui aqueous dispersions are going to interfere with the using a subcoating. P.O. Box 98427 core and lead to degradation in the core when Kowloon, Hong-Kong humidity sensitive drugs, e.g. aspirin or pancreatine, For information in advance: Please contact your local Fax: **852/23122261 are used. For this reason sometimes subcoatings BASF company or one of our regional centres.

Europe BASF Aktiengesellschaft LNF/FP – J550 News Mr. Peter Hoffmann D-67056 Ludwigshafen Germany Cremophor ELP: Monograph on “Purified Polyoxyl Fax: **49/62160-22627 35 Castor Oil” published in Pharmacopoeial Forum. NAFTA BASF Corporation The United States Pharmacopoeial Convention In addition to standard tests on Cremophor EL four published a new monograph on “Purified Polyoxyl additional specifications on acid-and peroxide value, Pharma Ingredients 35 Castor Oil” in volume 26, number 4 of the Pharma- water contents and limits of alcohol-soluble impurities Mr. Charles Dods copoeial Forum issued July–August 2000. are enclosed. 3000 Continental Drive-North Mount Olive, NJ 07828-1234 USA New Media Fax: **1/9734265355 South America 3rd edition of the CD-ROM BASF S.A. Fine Chemicals “Generic Drug Formulation/Kollidon”. Mr. Claudio Lehmann Caixa Postal 136 Since July 2000 a 3rd edition of the CD-ROM con- 09701-970 São Bernardo do Campo - SP taining the folder “Generic Drug Formulations” and the Brazil book “Kollidon – Polyvinylpyrrolidone for the Fax: **55/117512255 pharmaceutical industry” is now available.

In the “Generic Drug Formulations” more than 30 new Eastern Europe/Africa/West Asia formulations of different drug forms were included. BASF Aktiengesellschaft These formulations mainly are based on our new LRM/M – D 205 excipients like for example the Kollicoat grades, Ludi- Mr. Rolf Hanssen/Mr. Matthias Hof press LCE and the research product Kollidon SR. D-67056 Ludwigshafen Germany In the Kollidon book 15 new paper references were Fax: **49/62160-44689 added to the applications and some parts of the

analytical chapters were actualized (e.g. determina- Or visit our website: R10001e http://www.basf.de/pharma M

tion of monomers and formic acid). MEF