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Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.com by Procter & Gamble Co on 03/08/13 For personal use only.
Formulation of Specialty Tablets for Slow Oral Dissolution
Loyd V. Allen, Jr.
University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma, U.S.A.
INTRODUCTION Lozenges/Troches Dosage forms that dissolve slowly in the mouth, or that can be easily chewed and swallowed, are gaining in popularity, especially among pediatric patients. Hard (compressed or molded) preparations of this dosage form are called lozenges, troches, or drops. Soft (molded) lozenges/troches are often called pastilles, and chewable, gelatinbased lozenges/troches are often called gummy, novelty-shaped products. The term lozenge will be used in this chapter to refer to all variations of the dosage form.
DEFINITIONS/TYPES Lozenges are solid preparations that are intended to dissolve or disintegrate slowly in the mouth. They contain one or more medicaments, usually in a flavored, sweetened base. They can be prepared by molding (gelatin and/or fused sucrose or sorbitol base) or by compression of sugar-based tablets. Molded lozenges are sometimes referred to as pastilles while compressed lozenges are often referred to as troches. They are usually intended for treatment of local irritation or infections of the mouth or throat but may contain active ingredients intended for systemic absorption after swallowing (1). Molded lozenges have a softer texture because they contain a high percentage of sugar or a combination of a gelatin and sugar. Hard lozenges have hard candy bases made of sugar and syrup and often incorporate an adhesive substance such as acacia. Commercial lozenges are made on a tableting machine using high-compression pressures. Ingredients should be heat stable if they are to be incorporated into compounded lozenges. Recently, soft lozenges and chewable lozenges have been reintroduced into pharmacy and are enjoying increased popularity. Soft lozenges generally have a polyethylene glycol (PEG) base, whereas chewable lozenges have a glycerinated gelatin base. These dosage forms usually are chewed and are a means of delivering the product to the gastrointestinal tract for systemic absorption.
HISTORICAL USE Lozenges have long been used to deliver topical anesthetics and antibacterials for the relief of minor sore throat pain and irritation. Today, they are used for analgesics, anesthetics, antimicrobials, antiseptics, antitussives, aromatics, astringents, corticosteroids, decongestants, demulcents, and other classes, and combinations of drugs. In the 3rd edition of The Pharmaceutical Recipe Book (American Pharmaceutical Association, 1943), the following list of troche formulas was included (2); they were all sucrose-based with either tragacanth or acacia added; Ammonium Chloride Troches, Charcoal Troches, Cubeb Troches, Gambir Troches, Menthol Troches, Peppermint Troches, Phenolpthalein Troches, Potassium Chlorate Troches, Quinine Tannate Troches, Santonin Troches, Compound Santonin Troches, Sulfur and Potassium Bitartrate Troches, and Tannic Acid Troches. Soft lozenges are similar to a historical form of medication that is now making a comeback—the “confection.” Confections are defined as heavily saccharinated, soft masses containing medicinal agents. Their growing popularity is largely due to the use of polymers, such as the PEGs as the matrix for the dosage form (Figs. 1–3). Confections are easy to use, convenient to carry, easy to store (i.e., at room temperature), and generally pleasant tasting. PEG-based lozenges have a tendency to be hygroscopic and may soften if exposed to high temperatures. Consequently, storage in a cool, dry place is recommended for these lozenges. Today, a popular lozenge for pediatric use is the chewable lozenge, or “gummytype” candy product (Fig. 4). The gelatin base for these chewable lozenges is similar to
Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.com by Procter & Gamble Co on 03/08/13 For personal use only.
FIGURE 1 Different shapes of chewable lozenges of the PEG type. Abbreviation: PEG, polyethylene glycol.
Formulation of Specialty Tablets for Slow Oral Dissolution 363 Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. 20% gelatin. These lozenges were prepared by pouring the melt either into molds or out on a sheet of uniform thickness. Some of the earlier soft lozenges consisted of a gelatin or a glycerogelatin base. and 10% purified water. or glycerinated gelatin suppositories that consisted of 70% glycerin.com by Procter & Gamble Co on 03/08/13 For personal use only. . the historical glycerin suppositories. FIGURE 3 Chocolate-flavored soft chewable lozenges. FIGURE 2 Different types of chewable lozenges that can be halved if necessary.
FIGURE 4 Gummy-type chewable lozenges. The last step often included dusting of the product with cornstarch or powdered sugar to decrease tackiness. The dosage forms were then punched out using various-shaped punches.to 5-years-old children handle a lozenge. In a Swedish study on how 3. This provided support for further study on the use of the lozenge for topical oral delivery of fluoride for preventing caries (3). . they may contain active medications that produce a systemic effect. The lozenge can also be adapted to form a lollipop using a mold that allows the insertion of a stick. 5). pharmacists can prepare lozenges extemporaneously with minimal equipment and time.com by Procter & Gamble Co on 03/08/13 For personal use only. The lozenge dosage form has a number of advantages.364 Allen Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. both pediatric and geriatric. especially for patients who cannot swallow solid oral dosage forms. It is easy to administer to both pediatric patients and patients of advanced age. Medicated lozenges are usually intended for local treatment of infections of the mouth or throat. it has a pleasant taste. Lozenges are also used for medications designed for slow release. Also. APPLICATIONS Lozenges are experiencing renewed popularity as a means of delivering different drug products. it was observed that 62% of the children could keep parts of the lozenge in the mouth for at least 10 minutes. and it extends the time that a quantity of drug remains in the oral cavity to elicit a therapeutic effect. This dosage form maintains a constant level of the drug in the oral cavity or bathes the throat tissues in a solution of the drug. however. These lollipops can then be held in the mouth and removed as desired (Fig. These can be made using different molds for different types of patients.
One disadvantage of the lozenge is that children can mistake it for candy. ANESTHETIC FOR SORE THROAT Ambroxol Sucking lozenges containing 20 or 30 mg ambroxol hydrochloride has a beneficial painrelieving effect in patients with acute sore throat as it has local anesthetic properties (4. Parents should be cautioned not to refer to medications as candy and to keep the product out of the reach of children.com by Procter & Gamble Co on 03/08/13 For personal use only.5).0 and 12. antimicrobial. including colors and flavors. cough suppressants. ANTI-INFLAMMATORY FOR SORE THROAT Flurbiprofen Flurbiprofen lozenges have been found to be quite effective for treatment of sore throat at a dose between 5. and other effects for topical administration and for their ability to deliver hormones. especially in the area of their use as an anesthetic. anticariogenic. CONTEMPORARY STUDIES ON LOZENGES/TROCHES There are many reported contemporary research studies on the troche or lozenge dosage form. and other drugs systemically.Formulation of Specialty Tablets for Slow Oral Dissolution 365 Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. FIGURE 5 Example lollipops of different formulations. .5 mg (6–8).
and gentamicin) administered four times daily was found to be tolerable and microbiologically effective. The use of a xylitol lozenge after sucrose can be an advisable practice for fixed orthodontic patients to prevent future dental caries (20). The formulations containing noscapine base were without any appreciable base and fulfilled the requirement of taste acceptability and adequate release properties (30). clotrimazole. clotrimazole (12–14). Mucositis occurs in the majority of radiotherapy-treated head and neck cancer patients. Fluoride Many fluoride supplements sold in Norway are lozenge-type tablets. achieving elimination of Candida in all patients and a reduction in gram-negative flora in most patients (9). including various drugs and combinations as bacitracin. and gentamicin (BCoG) (9). DIURETICS Hydrochlorothiazide bioavailability was studied from a molded isomalt-based tablet administered orally and as a lozenge. . The use of zinc has been shown.com by Procter & Gamble Co on 03/08/13 For personal use only. and others (18). nystatin (17).11). those receiving hematopoietic marrow transplantation and in about 40% of all patients receiving chemotherapy. which allow for extended enamel exposure to fluoride (21. in a number of studies.366 Allen ANTIMICROBIAL Antimicrobial lozenges were removed from the pharmaceutical market by the Food and Drug Administration about 40–50 years ago but are now making their way back as subjects of additional research and approved drug applications.16). clotrimazole. The relative bioavailability of the dosage form Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.22). CARIES PREVENTION Xylitol Xylitol delivered by gum or lozenge appears to be effective clinically in reducing cariogenic bacteria and caries levels (19). BCoG lozenges (containing bacitracin. COMMON COLD-ZINC Zinc Lozenges Zinc lozenges have been found in studies to support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms (23). COUGH SUPPRESSANTS Noscapine Lozenges and chewing gum were evaluated as delivery systems for noscapine with the aim of developing improved antitussive preparations. Its limitations include its bad taste and possible side effects (24–29). amphotericin B (10. gramicidin/tyrothricin (15. to reduce cold duration and antibiotic use.
which were in the hyperandrogenic female range but resembled steady state pharmacokinetics (32). PAIN MANAGEMENT Fentanyl Oral Transmucosal Fentanyl Citrate (OTFC. In contrast. regular and full-strength oxidizing lozenges and a no-treatment control. Only the full-strength oxidizing lozenge significantly reduced the tongue dorsum malodor and yielded a significant increase in the modified oral rinse test. to residual oxidizing activity retained in the oral cavity (34). The use of the 4 mg nicotine . at least in part. Cephalon.4%. UT) is well tolerated and mucosal absorption avoids first-pass metabolism. testosterone. Estradiol. Direct molding of isomalt tablets may be a suitable technique to administer a poorly soluble drug either as a conventional tablet or as a lozenge (31). ORAL MALODOR A study on the use of anti-malodor properties of oxidizing lozenges. was undertaken.com by Procter & Gamble Co on 03/08/13 For personal use only. This study involved two brands of breath mints. progesterone. Progesterone.2% and as a swallow tablet was 89. HORMONES Testosterone Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. as compared to breath mints and chewing gum. and Dehydroepiandrosterone The pharmacokinetic profiles of estradiol. presumably due. with levels reaching upper limits of the male range. chewing gum with no active ingredients. Testosterone. SMOKING LOZENGES Nicotine Medicinal nicotine should be preferentially encouraged for smokers or smokeless tobacco users wishing to switch to lower-risk products (39. Their results showed the transbuccal route is a novel approach to providing therapy for the management of menopauserelated symptoms of postmenopausal women without the poor and often erratic systemic availability associated with other routes of administration (33). it was found that buccal absorption following administration of the lozenge produced a rapid and brief elevation of testosterone levels. In a study of 10 bilaterally oophorectomized women on the pharmacokinetics of testosterone following administration using transdermal gel or buccal lozenges. Actiq. topical gel absorption resulted in a prolonged elevation of testosterone levels. yielding a bioavailability greater than that of oral administration (35–38). and dehydroepiandrosterone in postmenopausal women following single and multiple dosing using a troche and the transbuccal route of administration was studied.Formulation of Specialty Tablets for Slow Oral Dissolution 367 administered as a lozenge was 106.40).
Chewing gum and lozenges were ranked equal in a study on the effect of chewing gum and lozenges in relieving the signs and symptoms of xerostomia in a 2-week crossover clinical trial in 18 rheumatic patients with dry mouth symptoms and low salivary flow rates (46). Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. OTHERS Human Interferon Human interferon alpha oral lozenges were studied in patients with hepatitis C(HCV). Patients were instructed to take one lozenge daily. V6 chewing gum and Salivin lozenges were ranked as the two best products by patients in a 106-patient study of patients with low salivary flow rate and a long history of dry mouth (47). Silver Acetate Silver acetate has been studied for a number of years as an aid in smoking cessation programs (43.368 Allen lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in smokeless tobacco users (41. The treatment was well tolerated and the patients reported and increase in drive and appetite as well as an improvement in their exercise tolerance (48). The results of the study suggest that one could expect from the ingestion of the lozenge to better cope with psychological and emotional stress (49). In a comparison of five saliva stimulation formulas. The authors concluded that a throat lozenge containing amyl metacresol and dichlorobenzyl alcohol could have significant effects in reducing the infectivity of certain infectious viruses in the throat and . extracts from hops. and oat). Herbal Lozenge A randomized double blind.44). placebo controlled trial of the electrical activity of the human brain was undertaken after exposure to a lozenge containing four different herbal preparations (lavender oil.com by Procter & Gamble Co on 03/08/13 For personal use only. Virucidal Lozenge A potent virucidal mixture of amyl metacresol and dichlorobenzyl alcohol at low pH inactivates enveloped respiratory viruses influenza A. respiratory syncytial virus and severe acute respiratory syndrome coronavirus but not viruses with icosahedral symmetry. lemon balm. This safe and simple intervention may provide clinical benefit to individuals with distressing dry mouth symptoms (45). on an empty stomach and retain it in the mouth until completely dissolved.42). XEROSTOMIA Salivary Stimulation Lozenges for Xerostomia Anhydrous crystalline maltose 200 mg lozenges administered three times daily improved salivary output and decreased complaints of dry mouth and eyes in patients at a total of 33 sites in the study. in the morning. such as adenoviruses or rhinoviruses.
placebocontrolled trial. An additional benefit was relaxation (51). Their primary disadvantage is the high temperature required for preparation.Formulation of Specialty Tablets for Slow Oral Dissolution 369 presumably in cough droplets. A portion of the active drug product may actually be absorbed through the buccal mucosa. Hard lozenges should not disintegrate but instead provide a slow. 120. The troches were administered prior to every meal for 4 weeks. They should have a smooth surface texture and a pleasant flavor that masks the drug taste. Capsaicin Lozenges Capsaicin troches were studied for swallowing dysfunction in the elderly. and 180 minutes (53). COMPOSITION Hard Lozenges Hard candy lozenges are mixtures of sugar and other carbohydrates in an amorphous (noncrystalline) or glassy condition. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.5%. Measurements included assessment of individual latency time of the swallowing reflex and cough reflex sensitivity. The results showed the throat lozenges containing magnesium chloride produced much more rapid and stronger benefits than from the inhalation and injection routes of administration. 60.com by Procter & Gamble Co on 03/08/13 For personal use only.52% menthol containing lozenges significantly altered the thermal sensory thresholds in the oral cavity (52). Visual analog scales were used and saliva was sampled and tested initially and after 30. Hard candy lozenges generally weigh between 1. Excipients such as sorbitol and sugar have demulcent effects.5 and 4. They found that daily capsaicin lozenge supplementation resulted in a significant improvement in upper protective respiratory reflexes. 90. Magnesium Chloride Lozenge Magnesium chloride (100 mg) throat lozenges producing 100þ mM magnesium ion concentration in saliva were tested to determine if they had any beneficial effects in asthma rescue and prevention as compared to inhaled and injected magnesium. Soft Lozenges Soft lozenges have become popular because of the ease with which they can be extemporaneously prepared and their applicability to a wide variety of drugs.5%–1. The bases . thus possibly reducing opportunities for person-to-person transmission (50). uniform dissolution or erosion over 5–10 minutes. The long-term effect of capsaicin and short-term effect of menthol lozenges on oral thermal sensory thresholds was studied. Radiation-induced xerostomia was effectively treated using pilocarpine 5 mg lozenges in patients with head and neck cancer.5 g. 150. The use of 0. particularly in the elderly with a high risk for aspiration (54). These lozenges can be considered solid syrups of sugars and usually have a moisture content of 0. which relieve the discomfort of abraded tissue caused by coughs and sore throat. This was a double-blinded. thereby escaping the first-pass metabolism that occurs when a drug is swallowed and absorbed through the gastrointestinal tract.
They are highly flavored and frequently have a slightly acidic taste. acacia. or similar materials. Remove the blank lozenges and weigh. and they can be either slowly dissolved in the mouth or chewed. by molding a matrix to form a soft lozenge. An alternative and older form of soft lozenges is the pastille. Obtain and melt sufficient lozenge base to fill 6–12 molds. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.370 Allen usually consist of a mixture of various PEGs. The calibration can be done as follows: 1. 3. is usually transparent. involves pouring the mass out to form a sheet of uniform thickness and then punching out the lozenges by using a punch of the desired shape and size. Hard lozenges are usually prepared by heating sugar and other components to a proper temperature and then pouring the mixture into a mold or by pulling the mass out into a ribbon while it cools and then cutting the ribbon to the desired length. a glycerogelatin. If the flavoring agent (an oil) is immiscible with the base. and an adjustment may be required in the quantity of the base used.com by Procter & Gamble Co on 03/08/13 For personal use only. 4. 5. Prepare the lozenge mold. In general. Novelty-Shaped Products) Chewable lozenges have been on the market for a number of years. depending on the intended effect of the incorporated drug. or an acacia: sucrose base. These lozenges are relatively easy to prepare extemporaneously. The powders contained in the lozenges may also occupy a specific volume. which is a soft lozenge. Chewable Lozenges (Gummy. These lozenges may be colored and flavored. and confirm that the cavities are clean and dry. Each approach is described. Chewable lozenges are especially useful for pediatric patients and are an effective means of administering medications for gastrointestinal absorption and systemic use. Use this weight as the calibrated value for that specific mold when using that specific lot of lozenge base. the quantity of flavoring agent added to medicated lozenges is about 5–10 times that used in candy lozenges to compensate for the flavor of the medication. Molds used in the preparation of lozenges must be calibrated to determine the weight of the lozenge using the applicable base. and consists of a medication in a gelatin. and trim if necessary. cool. Both soft lozenges and chewable lozenges are usually prepared by pouring a melted mass into molds. The most difficult part involves preparing the gelatin base. 2. Because their fruit flavor often masks the taste of the drug. . Another method. the glycerin solution is then incorporated into the product. These “dosage replacement calculations” are analogous to those used with suppositories. PREPARATION Lozenges are prepared by molding a mixture of carbohydrates to form hard candies. it can be dissolved in glycerin. or by molding a gelatin base into a chewable mass. Divide the total weight by the number of blank lozenges to obtain the average weight of each lozenge for this particular base. A commercial method is to compress the materials into a very hard tablet. they are an excellent way of administering drug products. Pour the molds. which depends on the ingredients.
a lozenge can increase the residence time of a drug in the oral cavity. A 0. The authors found that the presence of magnesium stearate decreased the availability of CPC in solution due to adsorption of CPC on to the magnesium stearate. suspensions. Preservatives have a tendency to partition into flavors. is as follows: tablets/capsules. The solvent technique often uses a ratio of 1 part solvent to 3–5 parts drug. The baseline flow rate for saliva of about 0. They found that borneol was more volatile than menthol and this information may be utilized to improve the quality of lozenges containing menthol and/or borneol (58). Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. Binders can be added at any of several steps in the process. . the odor of a 0. Binders are substances added to tablet or lozenge formulations to add cohesiveness to powders. literature or vendor information.6–2. Based on these calculations. and lozenges. there is about 1.3% w/ w of the lozenge weight (55). going from the most rapid to the slowest.07 mL of saliva resident in the mouth before swallowing and about 0.5 (56). The investigators concluded that cetylpyridinum chloride should be formulated at a pH greater than 5. Generally. particular product needs. wax content of the active layer and the composition of the bioadhesive layer were important variables affecting the performance of this lozenges (57). the rate of removal. their characteristics should be considered. Another study involved the pH at which cetylpyridinum chloride was most effective in a lozenge dosage form. chewable tablets.” or “face powder” sweet. and minimal aroma. According to salivary kinetics. A bioadhesive lozenge was studied consisting of an active layer and a bioadhesive layer.” “gauze pad. The frequency of swallowing is about 0. and individual preferences. because they are not always water soluble. and most flavors are oily in nature.com by Procter & Gamble Co on 03/08/13 For personal use only.3 times per minute.015% solution of propylparaben has a tongue-numbing effect. providing the necessary bonding that contributes to the maintenance of the integrity of the final dosage form. A 0. FORMULATION STUDIES The effectiveness of cetylpyridinium chloride (CPC) lozenges was studied with various excipients. Binders are usually selected on the basis of previous experience of the formulator. A study on the volatility of menthol and borneol was undertaken to determine the rates of vaporization of the two ingredients.3 mL/min may be increased to about 10.125% butylparaben solution has the least aroma of all. Dosage forms are removed from the mouth at various rates.71 mL after swallowing. They authors concluded that magnesium stearate should comprise not more than 0. If flavors and preservatives are included in the product formulation. The purpose of the dosage form was to prolong the effective levels of cetylpyridinium chloride in the oral cavity.6 mL/min when stimulated. solutions. producing a slight sting. depending on the specific procedure being used and the speed at which the lozenge should disintegrate. For example. PHYSICOCHEMICAL CONSIDERATIONS A binder is used in most lozenges.Formulation of Specialty Tablets for Slow Oral Dissolution 371 The same technique can also be used to incorporate an oily drug into a lozenge. The drug loading.08% solution of methylparaben has been described as “floral.
STORAGE/LABELING Lozenges (hard. therefore. either room temperature or refrigerated temperature is usually indicated.5 mg per lozenge. Considerations must. and an unpleasant aftertaste. as long as they are protected from moisture and heat. the length of time they will be stored. the storage conditions of the lozenges. as well as the appearance. generally provide a stable dosage form. An active drug assay can be done by a contract laboratory as well as a melting and dissolution test. 3. QUALITY CONTROL The weight and uniformity of individual lozenges can be easily determined and documented. It is extremely reactive with the aldehydic components of candy base and flavor components. and chewable) should be stored either at room temperature or in a refrigerator. Some materials are so unpalatable or irritating that they are unsuitable for this type of administration. and the potential for drug interactions. specific gravity. It is easy to incorporate into a candy base because of its melting point (122–124˚C) and solubility (1. it is best to slip this unit into a properly labeled. This measure is especially needed for chewable lozenges. Depending on the storage requirement of both the drug and the base. odor. Hexylresorcinol. These products should be kept in tight containers to prevent drying. and surface texture. and/or chemical compatibility. color. It is compatible with most flavors. .com by Procter & Gamble Co on 03/08/13 For personal use only.372 Allen The type of medication prepared as a lozenge is limited only by flavor. The following are examples of different active ingredients used in lozenges: 1. but a PEG base is compatible. sealable plastic bag. and it is stable over a wide pH range. No flavoring or “mouthfeel” problems are associated with this material because of its low dose and lack of appreciable flavor. hardness. As much as 90%–95% of available benzocaine may be lost when added to a candy base. Masking doses greater than about 2 mg per lozenge requires special considerations. If a disposable mold with a cardboard sleeve is used. thus. Hard candies are hygroscopic and are usually prone to absorption of atmospheric moisture.5 g in 1000 mL of purified water). 2. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. which can dry out and become difficult to chew. dose restrictions. The usual dose of benzocaine is in the range of 5–10 mg per lozenge.4 mg per lozenge. weight. The dose of dextromethorphan hydrobromide is about 7. soft. depending on the active drug incorporated and the type of vehicle used. The dose of hexylresorcinol is about 2. STABILITY Completed products are dry and. Lozenges should be stored away from heat and out of the reach of children. include the hygroscopic nature of the candy base. an anesthetic mouth feel. Dextromethorphan. It is somewhat susceptible to reaction with aldehydic components. Benzocaine. They should be protected from extremes of humidity. it does have a bitter taste. Conversely.
Acidulents. can be added to a candy base to strengthen the flavor characteristics of the finished product and to control pH to preserve the stability of the incorporated medication. sugar-free lozenges and orange juice were tested.5. PATIENT COUNSELING The patient should be counseled about the purpose of a hard lozenge. and magnesium trisilicate can be added to increase the lozenge pH to as high as 7.5–3 when acidulents are added. When the concentration of corn syrup solids is greater than 50%. Because the hard lozenges are designed to provide a slow. Formulations that contain between 55 and 65% sucrose or 35 and 45% corn syrup solids generally offer the best compromise in dealing with problems related to graining. continual release of the drug over a prolonged period of time. moisture absorption. They should be kept out of the reach of children.5–8. while maintaining a smooth surface texture as the lozenge slowly dissolves. Sucrose solids in concentrations greater than 70% tend to increase graining tendencies and the speed of crystallization. the formulator is faced with the challenge of developing flavor blends that mask any unpleasant taste produced by the medication. disagreeable taste. Two acidic. Soft and chewable lozenges are to be taken only as directed and should not be considered candy. A study was conducted to analyze the erosive effect of acidic lozenges and to compare them with that of orange juice. fumaric. but the speed at which this tendency occurs depends on the ingredients that are used.com by Procter & Gamble Co on 03/08/13 For personal use only. which is to provide a slow. but it may be as low as 2. It is advisable to . therefore. such as citric. All hard candy lozenges eventually become grainy. the highly concentrated sucrose solution that results can be bacteriostatic in nature and will not support bacterial growth. the patient should be cautioned regarding excessive use. and preparation time. the graining tendencies decrease. Because any water present would dissolve some sucrose. If the medication has a strong. uniform release of the medication directly onto the affected mucous membrane. sodium bicarbonate. the gelatin is dissolved in a hot mixture of the glycerin/water/ sorbitol solution in which the parabens have been previously dissolved. and bacterial growth can occur if they are not packaged properly. and malic acids. The paraben preservatives were discussed earlier. Increased moisture absorption increases product stickiness and causes the medications to interact. It was concluded that excessive consumption of acidic lozenges can have the potential to enhance existing dental erosion (59). Regular hard candy has a pH of about 5–6. preservatives are generally not needed. However. however. Hard lozenges should not be chewed. If the lozenges to be used are acidic. that taste should be minimized to enhance patient compliance. If the medication has no significant taste. SAMPLE FORMULATIONS Lozenge Vehicles For the following vehicles. flavoring will not be a problem. hard candy lozenges are hygroscopic. tartaric. Because lozenges are solid dosage forms. their water content may increase. but moisture absorption tendencies can increase. Calcium carbonate.Formulation of Specialty Tablets for Slow Oral Dissolution 373 Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare.
Cool.1 20 40 30 – 0. Hard Lozenges Rx Hard Sugar Lozenges Powdered sugar Light corn syrup Distilled water Active drug. mint extract. Cover the mixture and heat on a hot plate at a high setting until the mixture boils. Coat the mold to be used with a vegetable spray. 4. corn syrup.15 0. Uncover and remove from heat at 61˚C. 8.05 30 30 30 – 0. .05 qs 100 F 0.374 Allen use a tared vessel to determine water loss during heating.2 mL qs 1.0 g 1. and water in a beaker and stir until well mixed.05 qs 100 B – 20 20 50 – 0. Accurately weigh or measure each ingredient. Vehicle Ingredients Sodium saccharin (g) Gelatin (g) Glycerin (mL) Sorbitol 70% (mL) Solution Polyethylene Glycol 6000 Methylparaben (g) Propylparaben (g) Flavor oil (mL) Purified water (mL) qs USP Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. 9. 3.05 qs 100 G 0. and food coloring and stir until well mixed.05 qs 100 E 0.15 0. Calculate the quantity of each ingredient required for the prescription.05 qs 100 C 0. Do not stir the mixture until the temperature drops to 55˚C.15 0.05 30 30 26 4g 0.05 qs 100 Ingredient-Specific Formulations Sample formulations are presented to illustrate the differences in the types of lozenges and their applications. and label. 7. package.com by Procter & Gamble Co on 03/08/13 For personal use only.15 0. so that an appropriate amount can be replaced. One can start at about 9% and make adjustments as needed. The amount of flavor oil can be determined by trial-and-error taste tests. 6.05 30 30 25 5g 0. A 0.1 20 70 – – 0.15 0.15 0. These formulas can be adjusted according to the quantity of active drug to be used. example Mint extract Food coloring.15 0. Pour the melt into the molds. Quickly add the active drug. continue boiling for 2 minutes. 5.05 20 40 26 4g 0. green 42 g 16 mL 24 mL 1.05 qs 100 D 0. Combine the sugar. 2.
12 of the 50 mg. 5. Package and use for compounding. 3.56 g 3g 6. Package and label. wiping off the excess. Rx Sildenafil Citrate 25 mg Sublingual Troches (#24) Sildenafil citrate Aspartame Silica gel Acacia Flavor 600 mg 500 mg 480 mg 360 mg qs PEG 1450 22 g (will vary depending on mold and size of tablet used as the source of the drug) 1. Slowly add the powders with thorough mixing. 2.60 g qs Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. 4. Cool for approximately 90 minutes and remove from the molds. 6. 6 of the 100 mg tablets). Melt the PEG 1450 at a temperature in the range of 50–55˚C in a suitable beaker or other container. 2. Pour into a mold that has been previously sprayed with a vegetable-based oil. Accurately weigh each ingredient and obtain the required number of sildenafil citrate tablets (24 of the 25 mg. 3. Triturate all the powders together to obtain a small. Rx Pediatric Chocolate Troche Base Chocolate (good quality) Vegetable oil (bland) 60 g 40 g 1. Calibrate the lollipop mold for the formula. 1. Heat the vegetable oil by using low heat or a double boiler/water bath. Cool. 4. . 3. 2.com by Procter & Gamble Co on 03/08/13 For personal use only. Cool to approximately 45˚C.84 g 3.04 g 22. Weigh or measure each of the ingredients. Calculate the quantity of each ingredient required for the prescription. Calculate the quantity of each ingredient required for the prescription.Formulation of Specialty Tablets for Slow Oral Dissolution 375 Rx Anti-Gag Lollipops (36 Lollipops) Sodium chloride Potassium chloride Calcium lactate Magnesium citrate Sodium bicarbonate Sodium phosphate monobasic Silica gel PEG 1450 46. 8. In a mortar. triturate the sildenafil citrate tablets to a very fine powder.12 g 2. 7. Add the chocolate and stir until melted. Accurately weigh each ingredient.44 g 3. 10. uniform particle size. 5. Calculate the quantity of each ingredient required for the prescription. 9.
Cool a few degrees. 8. 4. 7.com by Procter & Gamble Co on 03/08/13 For personal use only. 5. 6. add the flavor(s). 2. 3. 3. Add the acacia powder followed by the steroid and mix well. Accurately weigh or measure each ingredient. Accurately weigh or measure each ingredient.61 g 5 drops 1.376 Allen 4. Allow to cool at room temperature. and pour into troche molds. and acacia and triturate further to a fine powder. Rx Polyethelene Glycol Troches PEG 1000 Active drug.8 g 0. Rx Polyethelene Glycol Troches with Suspending Agent PEG 1000 Active drug. 5. Calculate the quantity of each ingredient required for the prescription. Package and label. example Aspartame sweetener Mint extract Food color 10 g 1g 20 packets 1 mL 2 drops 1. 2. Calculate the quantity of each ingredient required for the prescription. Package and label. Add the powders from step 4 and mix well. Melt the Fattibase/cocoa butter at about 40˚C/35˚C. 9. 4. silica gel. Accurately weigh or measure each ingredient. Pour into 1 g molds and place in a refrigerator to cool and harden. 6. Add the aspartame. Store in a refrigerator. Melt the PEG 1450 to about 55–60˚C. 6. Package and label. Add the artificial sweetener and the cinnamon oil and mix well. Soft Lozenges Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. 7. 2. 5. Melt the PEG 1000 on a hot plate to about 70˚C and gradually add the active drug powder and the aspartame sweetener by stirring Add the coloring and flavoring and pour into troche molds. Rx Steroid Linguets *** mg Fattibase/cocoa butter Steroid powder Acacia Cinnamon oil Artificial sweetener 76 g ** g 3g 5 gtts 14 gtts 1. Calculate the quantity of each ingredient required for the prescription. . example Silica gel Acacia Flavor 34.37 g 0.5 g 4. Allow to solidify.
Over a 3-minute period.Formulation of Specialty Tablets for Slow Oral Dissolution 377 3. 6. add the flavor. Calculate the quantity of each ingredient required for the prescription. (Note: This formulation is based on a mold that weighs approximately 1. and label. 6.6 mL 0. Add the powder mix to the melted base and blend thoroughly. Cool to less than 55˚C. Accurately weigh or measure each ingredient. cool.) Rx Powdered Sugar Troches Powdered sugar Active drug. Accurately weigh or measure each ingredient. 2. package. Roll the mass into the shape of a cylinder and cut into 10 even sections (approximately twice the length of the diameter). 4. 6. Mix the acacia and purified water together in a mortar to form a mucilage. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. Heat a water bath to boiling. and mix well. and label. 3. Remove from heat. Allow to air dry. Pour into troche or cough drop molds. package. Heat the PEG 1000 until melted at approximately 70˚C. example Acacia Purified water 10 g 1g 0. stir and heat for 5 minutes. Sift the powdered sugar and active drug together and gradually add sufficient mucilage to make a mass of the proper consistency. Gelatin Base Glycerin Gelatin Purified water Methylparaben 155 mL 3. and refrigerate until used. 5.08 g 14–18 drops – . 2. add the purified water. Cool. 7. Continue to heat for 45 minutes. The formula can be adjusted to other mold weights. 8.4 g 21. 4. 5. 3. Blend the powders together until uniformly mixed. In a beaker. 4.7 g qs 1.44 g 1. glycerin.com by Procter & Gamble Co on 03/08/13 For personal use only. Rx Drug Product in Gelatin Base Gelatin base Bentonite Aspartame Acacia powder Citric acid monohydrate Flavor Active ingredient 43 g 800 mg 900 mg 720 mg 1.8 g. Calculate the quantity of each ingredient required for the prescription. 5. 7. and methylparaben. add the gelatin very slowly while stirring until it is thoroughly dispersed and free of lumps.
2. and label.5 g 0. 4. If the mixture congeals while pouring. Add the desired flavor and mix. it may be necessary to calibrate the specific mold being used and to adjust the formula before actual preparation. 3. Blend the fentanyl citrate. Cool. Accurately weigh or measure each ingredient. Mix thoroughly and pour into 1 g molds. Add the flavor concentrate and mix well.5 g 0. acacia powder. 5. 3. Pour into suitable molds and allow to cool. 8.5 g 0. package.884 mg 23. bentonite. 4. and citric acid monohydrate together. . 7. Package and label. Calculate the quantity of each ingredient required for the prescription. 7. Triturate the powders together and add to the gelatin base melt. Accurately weigh or measure each ingredient. Rx Fentanyl 50 mg Chewable Gummy Gels (24 Chewable Gels) Fentanyl citrate Chewable gummy gel base Bentonite Aspartame Acacia powder Citric acid monohydrate Flavor concentrate 1. Accurately weigh or measure the ingredients. it may be necessary to reheat and then continue pouring. Continuously mix and pour the melt into the pediatric chewable lozenge molds and allow to cool. aspartame. Melt the Polybase using gentle heat to about 60˚C. 2.378 Allen 1.65 g 10–12 drops 1. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. 2. thoroughly mix until evenly dispersed. Calculate the quantity of each ingredient required for the prescription. 4. 6. 5. 6.com by Procter & Gamble Co on 03/08/13 For personal use only. Incorporate the dry powder from step 3 into the base and stir until evenly dispersed. Heat the chewable gummy gel base on a water bath until fluid. 8. 7. Package and label. Calibrate the particular mold to be used for this product. 3. Add the morphine sulfate and the aspartame powders and mix well. Since mold capacities vary. Cool a few minutes and add flavor while the mixture is still fluid. Calculate the quantity of each ingredient required for the prescription. Rx Morphine 10 mg Troches (#24) Morphine sulfate Aspartame Flavor Polybase 240 mg 250 mg qs 24 g 1. 5.35 g 0. 6. Melt the gelatin base using a water bath.
27(2):117–23. Nahler G. Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. Zegarelli DJ. Kruezig F. 1):S8. Mejare I. 22. Miller K. Wang NJ. Evaluation of the dental plaque pH recovery effect of a xylitol lozenge on patients with fixed orthodontic appliances. Soto TG. 8. A comparison between the release of fluoride from sodium fluoride lozenges and bone meal tablets. Raymond K. Christian J.S. Rockville MD: U. Laukkanen E. Washington. Head Neck 2002 24(1):6–15. Infection 1980. Schutz A. double-blind. Fungal infections of the oral cavity. J Pharm Sci 1993. Sari Z. Muller A. Clin Pharmacol Ther 2002. Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Yap BS. de Mey C. placebocontrolled trials regarding the local anaesthetic properties. Cutis 1976 17(2):277–80. 52(3):194–9. Charlesworth A. Aicher B. Absorption of orally administered amphotericin B lozenges. Lorentzen B. Birkeland JM. Speight J. 18(4):149–53. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Gund HJ. Int J Clin Pract 2000. Commun Dent Oral Epidemiol 1976. 3. Randomized. Arzneimittelforschung. Epstein J. de Mey C.S. El-Sayed S. The Pharmaceutical Recipe Book. Int J Clin Pharmacol Res 1988. Pschorn U. Clinical proof of concept. Muller A. BMC Oral Health 2006. 4. Charlesworth A. 14. Arzneimittelforschung. Minish E. 16(1):106–8. 7. 2002. Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8. Christian J. Ching MS. 21. Heid DW. 20. Schachtel BP. 5. Watson N. Mashford ML. Salivary concentrations of amphotericin B following its use as an oral lozenge.75 mg: a randomized. Ramoglu SI. double-blind. Swed Dent J 1994. 56(2):95–100. 61(6):699–703. Riordan PJ. Fluride supplements and caries in a non-fluoridated child population. Featherstone JD. A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy. 2007:624. Salivary levels of gramicidin after use of a tyrothricincontaining gargle/mouth-wash and tyrothricin lozenges. Int J Clin Pract 2002. 6. 74(2):240–4. Pschorn U. 18. 4(4):140–1. Br J Clin Pharmacol 1983. Oropharyngeal candidiasis treated with a troche form of clotrimazole.. In vitro evaluation of the antimicrobial activities of selected lozenges. How do 3 to 5-year old children handle a lozenge? A clinical-experimental study. 26(6): 1069–89. de Vries-Hospers HG. Aicher B. Richards RM. 15. Ramer GN. Multidose flurbiprofen 8. Gibb IA. 1943. Parker JM. Community Dent Oral Epidemiol 1999. J Prosthet Dent 1989. Blagden M. Kreuzig F. Johnson GH. Sengun A. 52(4):256–63.Formulation of Specialty Tablets for Slow Oral Dissolution 379 REFERENCES 1. 17. DC: American Pharmaceutical Association. double-blind. Bury RW. Salivary levels of gramicidin after use of a tyrothricin lozenge and a tyrothricin gargle/mouth-wash. 2002. Homan HD. Arch Intern Med 1979. placebo-controlled study in UK general practice centres. Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. 8(4): 259–61. Nahler G. Vix JM. Christian J. Anonymous. 16. 15(6Suppl. Delivery challenges for fluoride. Malkoc S. 9. 2. placebo-controlled study of efficacy and safety. Fischer J. 8(2):63–5. 13.75 mg lozenges in the treatment of sore throat: a randomized. van der Waaij D. chlorhexidine and xylitol. Montes LF. 10. Int J Clin Pharmacol Res 1983. Taylor TD. Burns P. 19. Gillissen A. 139(6):656–7. 12. Peil H. Leksell E. Angle Orthod 2004. Clinical evaluation of a nystatin pastille for treatment of denture-related oral candidiasis. . Nimmo WS. 11. 54(8):49–6. Duran I. Pharmacopeia 30-National Formulary 25. Clotrimazole troches: a new therapeutic approach to oral candidiasis. Pharmacopeial Convention Inc. Otolaryngol Clin North Am 1993. Hay J. Peil H. 71(5): 375–80. 82(12):1218–20. Bodey GP. Xing DK. 3(2):65–70.com by Procter & Gamble Co on 03/08/13 For personal use only. Miller K. Matula C. 3rd ed. Morgan DJ. U.
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com by Procter & Gamble Co on 03/08/13 For personal use only.Pharmaceutical Dosage Forms: Tablets Downloaded from informahealthcare. .
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