Article

Tablet Formulation Design And Manufacture: Oral Immediate Release Application
Jayesh Parmar & Manish Rane Colorcon Asia Pvt. Limited

Abstract
Tablet is the most preferred oral dosage form, due to many advantages it offers to formulators as well as physicians and patients. However, the process of manufacturing tablets is complex. Hence, careful consideration has to be given to select right process, and right excipients to ultimately give a robust, high productivity and regulatory compliant product of good quality.

Introduction
Tablets are solid dosage forms containing medicinal substances with or without suitable diluents. They are the most widely preferred form of medication both by pharmaceutical manufacturer as well as physicians and patients. They offer safe and convenient ways of active pharmaceutical ingredients (API) administration with excellent physicochemical stability in comparison to some other dosage forms, and also provide means of accurate dosing. They can be mass produced with robust quality controls and offer different branding possibilities by means of colored film coating, different shapes, sizes or logos. The objective of this review article is to provide a comprehensive overview of the tablet core manufacturing process with emphasis on oral immediate release formulations, along with common excipients used.

Tablet Manufacturing
Tablets are compressed powders and their manufacturing is a complex, multistep process. The ultimate aim of these compressed solids is to easily disperse in gastrointestinal fluid, aid in complete absorption of API and, at the same time, offer stability to the formulation. The tablet manufacturing process can be broadly classified as granulation (wet granulation or dry granulation) and direct compression. Granulation is an agglomeration process to improve the flow, density and compressibility of particulate material by size enlargement and densification. Granulation can be achieved by the use of binder solution (wet granulation) or dry binder (dry granulation). Wet granulation is often chosen over dry granulation because of dust elimination, single pot processing, uniformity of API content (low dose API) and obtaining predictable granulation end point determination. Examples of wet granulation methods include fluid bed, high shear, pelletization techniques, such as extrusionspheronization, spray drying, etc. The quality of this solid oral dosage form is, as a general rule, primarily governed by the physicochemical properties of the powder/ granulation from which the tablets are composed. Dry granulation (roll compaction or slugging) involves the compaction of powders at high pressures into large, often poorly formed tablets or compacts. These compacts are then milled and screened to form a granulation of the desired particle size. The advantage of dry granulation is the elimination of heat and moisture in the processing. Dry granulations can be produced by extruding powders between hydraulically-operated rollers to produce thin cakes that are subsequently screened or milled to give the desired granule size.

Direct compression avoids many of the problems associated with wet and dry granulations. However, the inherent physical properties of the individual filler materials are highly critical, and minor variations can alter flow and compression characteristics, so as to make them unsuitable for direct compression. Excipients are now available that allow production of tablets at high speeds without prior granulation steps. These directly compressible excipients consist of special physical forms of substances, such as lactose, sucrose, dextrose, or cellulose, which possess the desirable properties of fluidity and compressibility. Some of the most widely used direct compression fillers are cellulose derivatives (e.g. microcrystalline cellulose), saccharides (e.g. lactose and mannitol), mineral salts (e.g. dicalcium phosphate, calcium carbonate), and partially pregelatinzed starch (Starch 1500®). Table 1 provides the advantages and limitations of different table manufacturing methods.

Types of Tablet
The tablet dosage form is a versatile drug delivery system. Different types of tablet formulations are available, which could be broadly classified based on: (1) route of administration such as tablets for oral delivery, sublingual delivery, buccal delivery, rectal delivery or vaginal delivery, and (2) formulation characteristics such as immediate release tablets, effervescent tablets, melt-in-mouth or fast dissolving tablets, delayed release or extended release tablets. In all the cases, the general manufacturing process, machinery used for preparation of tablets and materials used are similar. The process of manufacturing a robust tablet dosage form and consistently maintain its quality is a key challenge to all formulators. Hence the manufacturing process and formulation components take pivotal importance. Email: jparmar@colorcon.com mrane@colorcon.com

Tablet Components
Tablet dosage form is composed of two main ingredients: (1) API and, (2) inactive ingredients also termed as excipients. The different physicochemical properties of API and manufacturing process selected dictates addition of different types of excipients, depending on the specific function they provide to aid in manufacture of tablets, efficacy and stability of the product. Active Pharmaceutical Ingredients API play a very important role in selecting the excipients, method of manufacture, size of tablet, etc. Some of the important characteristics of API, which influence the tablet performance are listed in Table 2.

Pharma Times - Vol 41 - No. 4 - April 2009

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4 . Flow properties Bulk density Glucosamine sulphate has high bulk density. Metformin. Celecoxib. Solvent recovery issues. Lower particle size of API may be important for higher solubility and dissolution. disintegrants. L. the diluent selected should have high density and vice-versa in order to avoid segregation issues in a directly compressible formulation. regulatory compliant. whereas Chondroitin sulphate has low bulk density. Wet granulation Robust process suitable for most compounds. thus reducing segregation potential.Vol 41 . ~ 560 C) is known to cause tablet punch sticking.This includes. so good for unstable compounds. which can be classified as primary excipients based on their functionality or as secondary excipients based on the way they are used. support or enhance stability. for a high density API. Expensive: time and energy consuming process. Albendazole. Imparts flowability to a formulation. Primary excipients . generally limited to lower dose compounds. Ideally all the excipients must be chemically inert. fillers (diluents). Not suitable for all compounds. Melting point Ibuprofen (M. binders. 22 Pharma Times . Vacuum drying techniques can remove/reduce need for heat. Low solubility of API may dictate the choice of manufacturing process from dissolution point of view. non-toxic. compatible with API. Dry granulation (slugging or roll compaction) Eliminates exposure to moisture and drying.April 2009 . Needs organic facility. 2. Solubility Nifedipine. However. 4. Health and environment issues. glidants. Wet granulation (non-aqueous) Expensive equipment.Table 1 : Tablet manufacturing methods . Can reduce elasticity problems. economical process. Hence needs to be granulated for tablet preparation. Dusty procedure. Density plays a significant role in the blend uniformity of API along with other excipients. Binds API with excipient. this may give rise to capping problem in tablets. Limitations Not suitable for all API.P. They comprise the major part of a formulation and hold the key to its success. Segregation potential.low dose. Poor flow of API may lead to loss of tablet hardness and weight variation issues. Expensive excipients. have acceptable taste and be inexpensive. bioavailability or patient acceptability or Assist in product identification or Enhance any other attribute of the overall safety and effectiveness of the API product during storage or use (Blecher. Examples of API Misoprostol. Stability issues for moisture sensitive and thermolabile API with aqueous granulation. No heat or moisture. Aid processing of the system during manufacture or Protect. which may adversely affect dissolution and compaction. gliclazide have low solubility. In general. A wet granulation is the preferred method with such API.advantages and limitations Method Direct compression Advantages Simple. High dose may result in direct physical impact of the API on tablet roperties. Coating surface with hydrophilic polymer can improve wettability. 1. Excipients Pharmaceutical excipients can be defined as any substance other than the active API or pro-API that has been appropriately evaluated for safety and is included in API delivery system to either. Low melting point of API may result in sticking problems or soft tablets during compression. Paracetamol bulk powder has poor flow.high dose. Moisture content Ampicillin trihydrate formulation often cause tablet punch sticking problem. This may restrict the formulator to use granulation techniques or higher levels of lubricants/glidants to impart the flow. Acidic API having pKa (3-5) will solubilize at higher pH. meloxicam exhibit better solubility in basic pH. Particle size pKa Aspirin. It dictates the pH level at which ionization takes place and subsequent solubilization. Suitable for moisture sensitive API. paracetamol ..No. Specialized equipment required. Table 2: Effect of different physicochemical properties of API on the formulation Property of API Dose Effects on tablet formulation Low dose may have content uniformity effects. The pharmaceutical industry uses many different types of excipients. Slow process. High moisture content of API may result in sticking issues during compression of tablets. non-hygroscopic. 3. ramipril . lubricants. 1995).

Can be used in roller compaction and extrusion/ spheronization.Vol 41 . Disintegrant should be used in formulations. anhydrous material used for direct compression due to superior compressibility. whereas Aspirin is good. flavors. Examples of API Divalproex sodium and L-Carnitine. Highly compactable. film coating. Certain API's. Certain API are unstable to heat or moisture or light. May brown on aging/Maillard reaction. Potential laxative effect at high dose. Used at concentrations of 20 . stearate over blending.90%. low humidity conditions in processing area become critical for such API. have poor ability to compact and hence granulation techniques may be required as a means of formulation velopment. Compactability Secondary excipients .requires high levels of lubricant. Has some disintegrant properties due to wicking properties. Table 3 lists some of the commonly used diluents. The wet massing process and the drying of the granules can lead to a considerable decrease in compaction properties. Partly soluble in water. Insoluble. Inert. Clopidogrel Degradation profile Excipient compatibility Nifedipine is photosensitive.This includes. Negative heat of solution cooling mouth feel. sweeteners. Comments Available as anhydrous and monohydrate. The polymorphic trans formation may occur during manufacturing process due to application or generation of heat or presence of moisture. Diluents Diluent is added to formulation to increase the bulk volume of the active and hence the size of the tablet suitable for handling. Abrasive . Table 3: List of most commonly used tablet diluents Diluent Lactose Advantages Lactose deforms by brittle fracture. chemical stability or bioavailability. Very abrasive. MCC Very popular. Expensive. Rabeprazole is sensitive to heat and moisture. 4 . Non reactive. In general. These excipients are responsible for appearance and performance. however. Slowest dissolving sugar formulations need adequate disintegrant. Limitations Lactose intolerance. Good ability to compact renders ease in direct compression of tablets.No. Granulation does impart some plastic nature to the end product.April 2009 23 . Requires high levels of lubricant. Mannitol Non-hygroscopic. Incompatible with strong oxidizing agents. Soluble in water. Careful selection of manufacturing process. Can cause punch filming/ picking. Primary amine based API's are incompatible with Lactose (due to Malliard's reaction) Acetaminophen has poor ability to compact. Spray dried forms may contain amorphous material. It is not a reducing sugar and can be substituted for lactose (lactose not acceptable in certain markets). Formulating such API into tablets may be challenging. which may have differences in solubility. Bovine derived.90% usage level. Many different grades available. Excipient compatibility testing would help in selecting right excipient. The selection of the diluent will depend on the type of processing and plasticity of materials to be used. a direct-compression formulation will require a diluent with good flow and compaction properties. Non-abrasive. 10 . moisture content and bulk density is available. Less sensitive to Mg. Variety of particle size. Less sensitive to press speed.Property of API Hygroscopicity Effects on tablet formulation Highly hygroscopic API may result in problems such as tablet punch sticking. Pharma Times . Many grades available. Aspirin is incompatible with magnesium stearate. Certain API exhibit polymorphic forms. colors. Plastically deforming. Good compressibility. Has both plastic and brittle nature depending on grade. wetting agents. Polymorphism Desloratadine. Certain API may be incompatible with specific excipients and may limit their selection.

No. it may be advantageous to combine partial pregelatinized starch with MCC or lactose in a 1:1 ratio for enhancing tablet hardness.absorbed water may be responsible for hydrolysis of sensitive API. Today pharmaceutical companies increasingly use high speed tablet press for faster and higher productivity. Not used extensively in wet granulations. Excellent flow properties. Has better compaction properties than native starch.25%) 24 Pharma Times . key process and corresponding diluent knowledge has become important. or surface-bound or surfaceabsorbed water on the excipient. Figure 2 shows impact of tablet press speed on the tablet breaking force (hardness) when compressed at increasing compression pressure. Figure 1 gives loss on drying (LOD) and water activity coefficient of some commonly used filler. but very high water activity coefficient. 49. In general. Less susceptible to Mg. Can "trap" API under a cone or heap in a dissolution vessel. Formula 4 contains: Partially Pre-gelatinized Starch (Starch 1500®. stearate over-blending. Starch 1500 provides stable formulation. It can be seen that formulation with combination of MCC + Starch 1500 gives low yet acceptable hardness of tablets when compressed at higher speeds and at high compression pressures. 50%) + Magnesium Stearate (0. but very low water activity coefficient. This also means that the disintegration time is not affected for tablets compressed at higher compression pressure Compression Force (KN) Figure 2: Effect of Press Speed on Hardness of tablets compressed at different compression pressures. but free. Self lubricant and reduces requirement of lubricants.can cause accelerated tooling and machine wear. Partial pregelatinized starch Can be used up to 75% in wet granulation. Use of combination of diluents with synergistic properties or co-processed excipients. moisture content may indicate hydrate form or tightly bound water molecule of crystallization. are gaining significance in the pharmaceutical industry. 49. Used up to 50%.acts as binder and disintegrants. Dicalcium phosphate Practically insoluble in water. 50%) + Magnesium Stearate (0. Lactose. more specifically water activity coefficient of such diluents. has low LOD. may influence API stability since many API are prone to degradation by hydrolysis. For such high speed Water activity aw Mositure content Tablet Breading Force (kp) Diluents form a major portion of most of the tablet formulations due to newer high potency API's.Diluent Sucrose Advantages Sucrose serves as a dry binder (2-20% w/w) or as a bulking agent and sweetener in chewable tablets and lozenges. Deforms by brittle fracture. For direct compression. Globally accepted. Loses water of crystallization at elevated temperatures. Can be used up to 50% in direct compression. such as StarCap 1500®. Starch 1500 has very high LOD. Crystalline sucrose is free flowing. for instance. Non-hygroscopic.75%) +Microcrystalline Cellulose (Avicel® PH 102. Limitations Powdered sucrose is a cohesive solid.Vol 41 . Comments Sucrose is also available as invert sugar. Abbrasive .25%) Figure 1: Water activity Vs Moisture content of some commonly used fillers. whereas lactose or plain microcrystalline cellulose leads to higher impurity levels on stability (Cunnigham CR 2001). Available in milled and unmilled forms. Not recommended for use with poorly soluble API. soluble in acid but not alkali. Partial gelatinization improves binding yielding. The bound water may not cause hydrolysis of sensitive API.or surface. The moisture content. Hence. improved granule strength and enhanced tablet hardness. This free water is termed as water activity coefficient. tablet press.75%) +Microcrystalline Cellulose (Avicel® PH 102. 4 . for API such as Aspirin or Ranitidine that undergo hydrolysis.April 2009 . compressible sugar and as sugar spheres. Formula 3 contains: Dicalcium Phosphate Dihydrate (Emcompress®. Ability to compact is good and independent of machine speed. coprocessed starch excipient. On the other hand. Multifunctional . Tablets that contain large amounts of sucrose may harden over time to give poor disintegration.

the powder mixture is Figure 3: Effect of Press Speed on disintegration time (min) of granulated simply by tablets compressed at different compression pressures. Granulating agents are usually hydrophilic polymers that have cohesive properties that both aid the granulation process and impart strength to the dried granulate.Vol 41 . 4 .No. during high shear granulation. During compaction. Can be used for modulation of API release. Soluble in water and ethanol. Number of viscosity grades available for granulation. Acts as a multifunctional agent. Dry addition of binder is also possible in direct compression.April 2009 25 . which on standing increases in viscosity and becomes an important property to control. It is soluble in different solvent systems and suitable for both aqueous. However. non-aqueous or hydro-alcoholic solvents. Time consuming process. 2-8 Hydroxypropyl methylcellulose 2-8 Methylcellulose 1-5 May give hard granules. Starch 1500). The paste is prepared by suspending the starch in water and then adding boiling water with stirring. When the granulate dries. more Disintegration Time (min) Binder Table 4: List of some most commonly used binders Binders Typical concentration used (%) 5 . advantages and limitations. as a solution in the granulating fluid. high variability in preparation of starch paste. Small concentration required for effective binding.required mechanical strength. high hardness yet more free-flowing for tablet production. Partially pregelatinized starch Polyvinylpyrrolidone 5 . Table 4 lists some commonly used binders in the pharmaceutical industry with their typical concentrations. Gives harder tablets upon stability prolonging the disintegration time and dissolution of the active. May give hard granules especially if binder concentration and kneading time is increased. Starch paste is formed when starch grains are heated in water causing the rupture of the grains and release of the water soluble components.25 Advantages Limitations Native starch paste Good binding ability. the binders provide the cohesive binding and deformation characteristics necessary for the formation of tablets. hydroalcoholic mixture or an organic solvent to as shown in Figure 3 (Colorcon technical form liquid bridges followed by the drying data sheet). Binders form films on the surface of the granules. Inclusion of granulating agents or binders to increase granule strength is necessary. which can aid in the wetting of hydrophobic API. if added at too great a concentration. Starch paste has been widely used as a binder. Pregelatinized starch 5 . The acceptable disintegration time at a most common method of adding binders is reasonable compression force. Pharma Times . adding water. the films can form viscous gels on the granule surface and may retard dissolution. as to an API-filler mixture to ensure that powders and use water as the granulating granules and tablets can be formed with the agent in normal equipment or using fluid bed equipment. This property is important for process. polyvinyl pyrrolidone (PVP) and Binder is added during granulation step hydroxypropyl methylcellulose (HPMC). Only functions as a binder. The binder may vary the disintegration and dissolution and final performance of the tablet. This granulation process results in direct compression based formulations that powders of larger particle size and that are need low friability. Different suppliers have different gelatinization level. Paste is cooled before adding to the powder. so easier to prepare than starch. It is also possible to add polymers. the crystallization of any solids that had dissolved in the liquid will form solid bonds between the particles.15 Acts as binder and also as disintegrant. Compression Force (KN) Before tableting. Good binder. such as partially pregelatinized starch (e.g. Number of viscosity grades available for granulation.10 Cold water soluble. Available in range of molecular weight/ viscosities. The formulations with pregelatinized starch require separate disintegrating agents. Pregelatinized starch is an advanced. during high shear granulation. especially if binder concentration and kneading time is increased.

Amylose part of partially pregelatinized starch causes swelling and gives disintegrant action. such as the coating. and to break down the tablet into the primary particles as rapidly as possible. xanthan. etc Alginic acid. sodium starch glycollate and croscarmellose sodium. 1999). which could negatively affect the stability of moisture sensitive API (if the packaging does not provide adequate protection from the environment). 4 . once the tablet is taken by the patient. guar gum. sodium alginate Crospovidone Comments Probably works by wicking. One disadvantage with PVP is that it tends to reduce the viscosity of granulations and makes the determination of the granulation end point more difficult with certain type of instrumentation.List of some most commonly used disintegrants Typical Concentation used (%) 5 . Swells on contact with water.user-friendly version than native starch paste. etc. Table 5 gives list of some disintegrants commonly used in tablet formulations.Vol 41 . Most pharmacopeias include a disintegration test which can be applied to tablets and the detailed monograph is given in the pharmacopeias. Recent trend in pharmaceutical industry is towards use of Figure 4: Effect of different disintegrants on the physical properties of Hydrochlorthiazide tablets (Tablet are composed of Hydrochlorthiazide. loses disintegrant action when highly compressed. The tablet produced with PVP as binder also increases disintegration time and retards the API release over time. sometimes unsuitable for formulations containing moisture sensitive or hygroscopic API.. thus limiting concentration that can be used.25 2 . Higher concentration of such superdisintegrants also causes problems during aqueous film coating. forms viscous gels that can retard dissolution. Figure 4 shows influence of disintegrating agent on disintegration time of tablets. Strong wicking tendencies with some swelling action. or added dry to powder blends and granulated with water. including native starch.April 2009 . in general. sodium starch glycolate. Therefore. The positioning of disintegrants within the intra. which display excellent disintegration activity at low concentrations than native starches. A next generation product is partially pregelatinized starch. The compaction properties of many disintegrants. xanthan gum. 10 . and it is versatile and inert material. such as crospovidone. Tablets must have sufficient strength to withstand the stresses of subsequent manufacturing operations. ethanol or hydro-alcoholic mixture.10 Disintegrant Native Starch Partially pregelatinized starch MCC Insoluble ion exchange resings Sodium starch glycolate Croscarmellose sodium Gums such as agar. Swells like gums. 26 Pharma Times . crospovidone and certain ion exchange resins. Table 5 . since this material may be incorporated as a dry powder and granulated with water. High wicking activity. Lactose spray dried.10 2-8 1-5 <5 Disintegrant Disintegrant is included in the formulation to ensure that the tablet breaks up into small fragments in contact with liquid. magnesium Stearate and disintegrants) powerful disintegrating agents (superdisintegrants).10 5 . have high moisture sorption tendency. Figure 5 depicts the moisture vapor sorption graph for different disintegrants (Cunnigham CR. Major limitations of these superdisintegrants are relatively high cost and hygroscopic nature. and distribution process. such as croscarmellose sodium. It is also possible to prepare slurry and use it as a granulating agent. but forms less viscous gels than guar gum. lower viscosity grades are preferred for wet granulation. To overcome the cohesive strength produced by the compression process. Dicalcium Phosphate. often giving rise to orange peel effect to the coating. it must break up rapidly to ensure rapid dissolution of the active ingredient in 4-6 1-5 immediate release preparations. However. HPMC is soluble in both water and ethanol.No. Free flowing powder that swells rapidly on contact with water. PVP is a versatile binder used as solution in water. Starch was the first disintegrant used in tablet manufacture. swelling minimal at body temperature. Strong wicking action. Swells on contact with water. are not satisfactory and use of high concentration can also reduce tablet strength.and extragranular portions of granulated formulations can affect their water uptake and disintegration time. Superdisintegrants. disintegrants are added to the tablet formulations. Level of gelatinization is a key to product performance. This product offers disintegrant property along with binding capacity. Generally. packaging.

Starch has also been used as a glidant. These are materials with very small (10 nm) spherical particles that act as dividing cohesive particles to provide their glidant properties. Soluble. Die-wall lubricants can be divided into two classes: fluid and boundary lubricants.2 . partially soluble. poorer lubricant activity than fatty acid ester salts.April 2009 27 . and are commercially available under diverse brand names. Pharma Times . C Figure 5: Moisture uptake isotherms for powders of different disintegrating agents. Hydrophobic.5 .3 Sodium benzoate Fluid lubricants Light mineral oil Hydrogenated vegetable oil Stearic acid Glyceryl behenate 1-3 1-5 0.Crospovidone % Weight Change Socium starch glycolate Crosslinked CMC Starch 1500 adherent. Hydrophobic. Soluble. lubricant and wetting agent. and reduced tablet strength. anti-tacking agent. Metallic stearates are the most widely used boundary lubricants. can be applied to either formulation or tooling.2 . Boundary lubricants work by forming a thin solid film at the interface of the die and the tablet. For a robust formulation. variable properties between suppliers. also acts as wetting agent.4 2-5 Hydrophobic. widely used as lubricant and diluent Has small particle size and large surface area for good flowability. used at higher concentrations as controlled release agents. 4 . crystalline powder.No. too high levels resulting in decreased wetting of the tablet and a subsequent reduction in the rate of dissolution. which enhance flow property of powder blend by overcoming powder cohesiveness. reduce interparticle friction during compression and. also used as controlled release agent.2 0. The level of talc that can be added to a formulation is restricted by its hydrophobic nature. The oily lubricants may give a mottled tablet appearance due to uneven distribution. Table 6 gives list of some commonly used lubricants in the tablet formulations.List of some commonly used lubricants in tablet formulations Disintegrant Typical Concentation used (%) Comments Glidant Talc Fumed silicon dioxide 1-5 0. Anti-adherent % Relative Humidity at 25 deg. Soluble.4 Hydrophobic. to improve flow of powder blend on the machine and into the die cavity. Native starch powder is used as glidant and also as disintegrant. which reduce the friction between the tablet surface and the die wall during and after compaction to enable easy ejection of the tablet. concentration. Native starch Sodium lauryl sulfate Boundary lubricants Magnesium stearate Calcium stearate 1 . used for adsorbent.2 Polyethylene glycol 4000 & 6000 Sodium lauryl sulfate 2 .25 . Lubricants can be further classified into three types based on their detailed functionality: (1) glidant. Talc is traditionally one of the most commonly used glidants. and (3) die wall lubricant. poor powder flow due to their tacky nature.1 . disintegrant and glidant.10 0. Less hydrophobic than metallic stearates. Hydrophobic. These are typically mineral oils or vegetable oils. Hydrophobic. Fumed silicon dioxides are perhaps the most effective glidants. Acts as wetting agent.5 . They are available in a number of grades with a range of hydrophobic and hydrophilic forms. prevent sticking of powder on punch faces (anti-adherence). (2) antiadherent. having the additional benefit of being an excellent anti- Table 6 .0. The use of large amounts of starch can also aid the disintegration properties.2 0. and they may be either added to the mix or applied directly to the die-wall by means of wicked punches. Anti-adherent causes reduction in adhesion of powder to punch faces and thus Lubricant Lubricants are used in formulations to aid in smooth ejection of tablet from die cavity. Sodium stearyl fumarate 0.20 1-3 Magnesium lauryl sulfate 1 . Anionic surfactant.5 .2 0. which reduce the friction between the tablet punch faces and tablet punches. Fluid lubricants work by separating moving surfaces completely with a layer of lubricant.Vol 41 .5 Fine. order and duration of mixing of lubricant in the formulation. careful consideration has to be given in selecting right type.

Vol 41 . Magnesium stearate. Lactose. Figure 7 gives the effect of magnesium stearate on release profile of Hydrochlorthiazide.25% to 1. It should be remembered that the requirements for lubrication and anti-adherent may be very different when tablet presses are run at laboratory scale and at production scale. The effect increased as a function of the compression force. Excipient selection The selection of excipients is influenced by range of interrelated factors. Starch 1500®.April 2009 . However. like properties Properties of excipients Stablity (chemical & physical) Hygroscopic Compatible Particle size Availability Cost Regulatory acceptance Manufacturing process requirement Direct compression Wet granulation Fluid bed granulation Spray drying Extrusion & spheronization Other novel process Figure 7: Effect of Magnesium Stearate on Dissolution of Hydrochlorthiazide helps in preventing sticking. Also. then lubricant may form a hydrophobic film around the disintegrating Properties of drug Dose Solubility/ pKa Particle Size/ Shape Melting Point/ Thermal Stability Flow Properties Densities Selection of excipients for solid oral dosage forms Desired release characteristics Immediate release Sustained release Modified release Figure 8: Factors affecting the selection of excipients. MCC. readily forms a thin film on the diewall surface.Tablet Breading Force (kp) agent and ultimately result in prolonging disintegration time. at even 1% concentration. both objective and subjective. 2000). As the concentration of magnesium stearate increased from 0. Other excipients Certain excipients. Dicalcium Phosphate. are used only in situations where they are expressly needed to ensure the stability or performance of the product.0% the tablet breaking force reduced. a boundary wall lubricant. the addition of lubricant should be at the end of the mixing process. Thus they are most often used in combination with other lubricants to improve overall performance during compaction. when stearic acid was used. the major limitation to such combinations is high concentration required to give good lubricant properties in comparison to magnesium stearate. These materials do not influence ejection force or residual force. When formulation contains disintegrating agents. 28 Pharma Times . Also. All the factors. higher concentration of magnesium stearate can retard the dissolution of API due to its hydrophobic nature. Compression Force (KN) Tablets contained Hydrochlorthiazide. However. due to hydrophobic nature. lubricant. The level of a lubricant required in a tablet is formulation dependent and can be optimized using an instrumented tableting machine. If both lubricant and disintegrant are added together. Figure 6 gives the effect of different concentration of magnesium stearate on the breaking force of Hydrochlorthiazide tablets (Cunnigham CR. Formulation containing high concentration of magnesium stearate may result in tablets of reduced hardness. This results in reduction in powder ability to form strong compacts. it can hinder disintegration and dissolution performance of tablets. even if the compression force is increased. 4 . Figure 6: Effect of different concentrations of lubricants on the tablet breaking force Many pharmaceutical companies use combination of talc and stearic acid or talc and hydrogenated vegetable oils as an alternative to magnesium stearate. the tablets produced were increased with compression pressure. No single lubricant provides all the balanced functionality of each individual class of lubricant. like anti-oxidants and surfactants.No.

. pg 6 . K. AAPS. 4 . play an important role in making a decision [Figure 8]. When liquid flows over the surface of the formulation. Kadtare A.. Cunnigham C. C. The ActiPix Dissolution Imager is "a powerful tool that can reduce the time it takes a drug to come to market. Ed. Biotechnology.in real time . For example. Rudnic. K. October 1999. Paraytec says the instrument offers formulation scientists an alternative to "highcost. R. 2002. Bibliography And References Blecher. and Scattergood.April 2009 29 . Marcel Dekker Inc. Tablet holder enables accurate analysis The instrument combines a specially designed tablet holder and Paraytec's ActiPix D-100 UV area imager. and E. Owen SC (Ed. to understand the mechanism of drug release behaviour. Dibasic calcium phosphate replacement with Starch 1500® in a direct compression formula.The important components. R.of API and excipients." said Paraytec.). The holder is placed inside the ActiPix D-100 which enables real time recording and review of data.. batch-to-batch uniformity of product. K. R. K. Sheskey PJ. for example by quantifying protein aggregation. complex techniques such as terahertz spectroscopic imaging and magnetic resonance imaging "as they investigate the release of active compounds from dosage forms. Optimizating lubricant usage in a direct compression hydrochlorthiazide Real-time analysis of tablet surfaces Phil Taylor UK company Paraytec has introduced a new instrument designed to allow formulation scientists to visualise .. Evaluation of partially pregelatinized starch in comparison with superdisintegrants in a direct compression hydrochlorthiazide formulation. and Scattergood L. Cunnigham C. the choice of manufacturing method depends on the infrastructure available with the company. Excipient Development for Pharmaceutical. The ActiPix D-100 instrument has been used in a number of other applications in the pharmaceutical industry.called the ActiPix Dissolution Imager . and API Delivery Systems. Paraytec spun of from University of York Paraytec was spun out from the University of York to develop a series of instruments based on miniaturised ultraviolet-visible (UV-vis) absorbance detectors and capillary-based fluid handling technology. AAPS. Chaubal M. even quality of service offered by supplier. L. The effect of Starch 1500® on the stability of aspirin tablets stored under accelerated conditions.. and Scattergood L. including enzyme assays and protein sizing. Kottke. Pharma Times . K. Informa Healthcare. are also important parameters to be considered.. and Scattergood L. desired release characteristics and even manufacturing process. Paraytec has also been developing the technology for in-line testing in bioprocessing. Use of Starch 1500® to improve the uniformity of a low dose direct compression chlorpheniramine formulation. as this regulates the performance of many solid pharmaceutical dosage formulations. L. Excipients . Do N.. AAPS. October 2000.Vol 41 . regulatory acceptance.7. "It is important . 1995.. Cunnigham C. October 2000." according to a Paraytec statement. K. 2006. chapter 10 . Colorcon Technical Data Sheet. suitability and availability of excipient also play an important role. formulation containing a plastically deforming excipient. Fourth edition. UV absorbance detection is a laboratory technique widely employed to characterise and determine the levels of substances which dissolve in water and other liquids. Process. October 2001. Nov. R. In the present scenario. M. M. Banker GS. 12 (1). release of the active ingredient can be quantitatively monitored directly at the tablet surface.Tablet dosage form in Modern Pharmaceutics. Pharm.what is happening at a tablet surface when it dissolves. The new device . 2006. And finally.. 2005..No. October 1999. USA.. Rhodes C. Rowe RC. Pharmaceutical Press and American Pharmacists Association. Fluid bed granulation of Acetaminophen: Effect of key process variables on granule and tablet characteristics. It also depends on the dose of API and its physicochemical properties. Cunnigham C. R. with light absorbed at different wavelengths in the ultra-violet region indicating different compounds.was introduced to the marketplace at Pittcon on March 9 and could make it easier for drug developers to develop controlled-release medications.. AAPS. AAPS. Farrel T. associated cost and may be personal preference or experience. and Scattergood L. Control of dissolution rate of immediate release tablets containing Starch 1500® with a combination of different types and grades of Methocel™. Pharmaceutical Excipients. AAPS. thereby offering significant potential gains in earnings. Cunnigham.

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