Pharmaceutics Case Studies RVW

7.Describe how the surface area of a powder is affected by particle size reduction. Cite your basis.

"The reduction in the particle size of a solid is accompanied by a great increase in the specific surface area of that substance." In other words, as particle size decreases, the surface area increases - As a drug is reduced in particle size, the total surface area increases because a larger number of smaller particles allows for more overall surface area to be exposed.

Place the following list of processing steps in the correct order (i.e., from the beginning of the process to the end of the process) for use in the pharmaceutical manufacturing process for your film-coated tablet dosage form.

<Weigh drug substance and excipients> → <prepare the damp mass (ie., wet granulate) of the drug substance/ excipient blend> → <dry the granulation> → <add lubricant and glidant> → <Compress the final blend into bilayer tablets> → <coat the bilayer tablet>.

13. How does film coating a tablet affect the dissolution of drug from the dosage form as compared to the uncoated dosage form?

A film coating allows more control of the dissolution of the drug in different parts of the digestive tract. The coating itself can be modified to allow the controlled dissolution of the tablet either through an extended release or a timed release in the stomach or later on in the lower intestine depending on the intent of the drug. An uncoated dosage form is exposed to the digestive elements of the body immediately and has it's primary absorption quickly and in the stomach. Also an uncoated tablet lacks the slickness than allows coated forms easy passage through the mouth and esophageal tract down to the stomach

7. Dissolution of a drug from an oral dosage form is a significant problem for many drugs in pharmaceutical development. Explain how dissolution of a drug from an immediate release tablet may be a rate-limiting step in the absorption of the drug using citations other than Ansel's text.

Dissolution is affected by surface area, concentration gradient, physicochemical properties of the drug, formulation of the drug, and others. Drugs are separated into four different classes with different solubility and permeability characteristics. Class 2 drugs are low solubility, high permeability drugs. These drugs have dissolution as a rate limiting step; this is because the drug is not very soluble, which hinders the breaking up of the tablet in the body and therefore the release of the drug to be absorbed.

FENTORA® tablets are supplied in individually sealed, child-resistant blisters. In the medication guide for FENTORA®, the following points need to be addressed in counseling the patient on the medication storage: - "Keep FENTORA® in the original blister unit." Explain why the dosage form must be kept in its original blister (vs. being removed and stored in a temporary container, such as a pill box.) Cite your basis

FENTORA must be kept in the original blister because moving it into a temporary container, such as a pill box, can cause FENTORA's tablet integrity to be compromised. Moving FENTORA to a temporary container also increases the risk of accidental exposure to the tablet.

7. Based on the Noyes-Whitney Equation, list the parameters that influence the rate of dissolution of a drug substance in an aqueous media.

The Noyes-Whitney equation (dM/dt = (DACs)/h) describes the rate of dissolution of a drug substance in aqueous media (dM/dt) as being influenced by the diffusion coefficient (D), the total surface area of the device or gut (A), the aqueous solubility of the drug (Cs), as well as the height(width) of the boundary /diffusion layer (h). The equation can be used to describe how passive diffusion of a drug occurs across the biological membrane such as that in the GI tract.3

Describe the USP method for disintegration testing (USP chapter <701> disintegration). Cite your source.

The USP method for disintegration testing is used to determine whether capsules disintegrate within the prescribed time when placed in a liquid medium at the experimental conditions used. The test used is with the uncoated tablets. 1 dosage unit is placed in six tubes of the basked. Use the apparatus using water or the specified medium as the immersion fluid maintained at 37 +/- 2. At the end of the time specified, life the basket from the fluid, and observe all tablets: all of the tablets should have disintegrated completely. If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets. The requirement is met if not fewer than 16 of the total of 18 tablets tested are disintegrated

6. Identify the dosage strength (i.e., the amount of drug per dosage unit) and administered dose (i.e., total amount of drug given at each administration time) of the FDA approved marketed dosage form (from Question 2.)

The amount of drug contained in each marketed dosage unit is 1.2 grams. "The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is two to four 1.2 g tablets taken once daily with a meal for a total daily dose of 2.4 g or 4.8 g. The recommended dosage for the maintenance of remission is two 1.2 g tablets taken once daily with a meal for a total daily dose of 2.4 g."

. Identify the dosage strength (i.e., the amount of drug per dosage unit) and administered dose (i.e., total amount of drug given at each administration time) of the FDA approved marketed dosage form (from Question 2.)

The amount of drug contained in each marketed dosage unit is either a 6.25 mg tablet or a 12.5 mg tablet. The total amount of drug given at each administration time is 6.25 mg (females) or 6.25-12.5 mg (males) immediately before bedtime; maximum dose: 12.5 mg daily.

Identify the dosage strength (i.e., the amount of drug per dosage unit) and administered dose (i.e., total amount of drug given at each administration time) of the FDA approved marketed dosage form (from Question 2.)

The dosage strengths available for ABILIFY DISCMELT® are 10 mg and 15 mg. The total amount of drug given at each administration time ranges between 10 mg - 30 mg.

Identify the dosage strength and administered dose Identify the dosage strength (i.e., the amount of drug per dosage unit) and administered dose (i.e., total amount of drug given at each administration time) of the FDA approved marketed dosage form (from Question 2.)

The dosage strengths available for FENTORA® are 100 mcg, 200 mcg, 400 mcg, 600 mcg, and 800 mcg. The total amount of drug given at each administration time start at 100 mcg with no maximum dose.

A patient comes to your pharmacy with a prescription for a compounded alternative to FENTORA®. The physician is requesting that the tablet be formulated so that the tablet is not easily dislodged from the buccal cavity during administration. How might this be achieved (i.e. what additional excipient(s) would you use)? What benefits might you expect to observe with this new compounded formulation?

The drug should be formulated as a biodadhesive patch so that it is not dislodged easily from the buccal cavity. This would require an excipient such as chitosan that would serve as a bioadhesive. This formulation would also provide the benefit of more drug being absorbed through the mucosal lining because less would be lost in the saliva and swallowed, where it would be subject to first pass metabolism.

13.Effervescent granules are a type of powder/granule dosage form. Explain to a patient the mechanism of effervescence.

When water is added to the drug, two different chemicals react with each other and release a gas called carbon dioxide, which is responsible for carbonation, or a fizzy action. This makes the medicine taste less bitter. - Effervescence is when bubbles or fizz form as the result of carbon dioxide being produced and released. In beer it is the result of yeast eating the sugar. In an antacid it is the result of an acid and base coming together, specifically citric acid and sodium bicarbonate. They combine to form water, sodium citrate, and the carbon dioxide that is then released

Would you expect to see indistinguishable absorption from buccal versus sublingual for drugs other than fentanyl citrate?

Since both the buccal and sublingual areas of the mouth are made of similar lining mucosa it could be reasoned that all drugs will absorb indistinguishably across these surfaces. The rate of absorption, however, may vary between drugs depending on whether the drug is of a hydophillic or lipophillic nature

13. Describe an anti-counterfeiting technology applied at the dosage form level (i.e., not the packaging) used to prevent counterfeiting of the drug product.

Some companies will seal their capsules with an extra band of colored gelatin. The way in which this band is sealed makes the band extremely difficult to remove and replace without special equipment. Therefore, it is relatively tamper evident. - A special distinctive odors can be added into the tablet's film coating to provide a novel smell that helps identify if a drug is counterfeited.

ABILIFY DISCMELT® is based on the Flashmelt oral dosage formulation technology which is described in U.S. Patent No. 8,518421. This system utilizes superdisintegrant excipients that allow for rapid disintegration of the tablet. Explain, why an oral disintegrating tablet was designed, even though an oral immediate tablet was already approved and marketed? Cite at least one reference that is NOT Ansels or Remington.

The Flashmelt oral dosage formulation technology allows the rapid dissolution of Abilify Discmelt in a more immediate manner than the oral immediate tablet. This dosage form is also advantageous for administration-of medication to non-compliant patients or patients who may find it difficult to swallow an intact dosage form, or when rapid administration is required and no water is present. This is important because this medication is indicated for a number of psychiatric conditions.

13. Venlafaxine Extended Release Tablets are not bioequivalent to Effexor XR. Why not? Cite your basis using at least two references that are not Ansel's.

-Venlafaxine has a higher Cmax and earlier T max than Effexor XR. Venlafaxine also ha fluctuans in plasma concentrations are lower than with Effexor. In addition, Effexor XR provides a slower rate but the same extent of absorption. ** so we got full credit but TA's notes: " Good use of PK parameters; however, these two can meet BE when dosed under fed conditions. What about the release mechanism of each dosage form might make them produce different/variable release profiles under fasted state?" Venlafaxine Extended Release tablets are not bioequivalent to Effexor XR because Venlafaxine ER is made in the form of an osmotic system, so that it uses osmotic pressure to deliver the drug at a controlled rate over 24 hour. Effexor XR is not an osmotic system it is a different type of extended release that uses small spheroid beads in the capsule that are each coated with a water-insoluble, water-permeable film (hydrophilic matrix system). Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug.

Aripiprazole (ABILIFY DISCMELT®)

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Fentanyl citrate (FENTORA®)

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Mesalamine (Lialda)

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Xerostomia (i.e. dry mouth) is characterized by decreased salivary production. You are on rounds with a medical team and the physician prescribes ABILIFY DISCMELT®. However, you are aware that the patient has xerostomia, but this was not discussed on rounds. How would you advise the nurse to administer ABILIFY DISCMELT®? Cite your basis.

...

7. Some modified release oral tablets may be broken/split prior to oral administration without altering the modified release of drug, while others may not. Describe one example of each and explain the difference between them in terms of this property. Cite your basis not using Ansel's.

A system of modified release that can be split is hydrophilic polymeric matrix. Specifically, an example of a modified-release tablet than can be split is isosorbide mononitrate extended-release tablet. Isosorbide mononitrate extended-release tablet is made of a hydrophilic matrix system. Because this tablet is scored, the drug can be split because the extended-release excipients within the tablet are uniformly dispersed. As a result, the extended-release properties of the drug would still be functional, even after the drug was split or broken. A system of modified release that cannot be split is an osmotic pump delivery system. These drugs have a semi-permeable outer core that controls the release of the drug through a small laser-bored hole in one part of the tablet. The release is dependent on the use of an osmotic pressure gradient. If this tablet was split or broken, the environment created by the semi-permeable membrane would be destroyed, and the drug would have immediate access to the GI tract for dissolution. An example of such a drug would be Procardia.

ABILIFY DISCMELT® orally disintegrating tablets (ODTs) are manufactured using conventional tablet processes. They have different packaging requirements compared to other ODTs such as Zyprexa Zydis™ and Zofran ODT™. Describe why the packaging, handling, and friability of ABILIFY DISCMELT® ODT is different than ODTs made by lyophilization processes

ABILIFY DISCMELT is manufactured using the conventional tablet process. With the conventional tablet process, the result is a fast-disintegrating tablet with adequate hardness for packaging in bottles and easy handling. Due to the increased hardness associated with conventional tablet processing, tablets can be packaged in plastic bottles rather than limited to blister packs. The lyophilization process used for Zyprexas Zydis and Zofran ODT makes the tablets more friable as compared to being prepared by the conventional method. The tablets prepared by the lyophilization process are more likely to be packaged in blister packs in order to prevent damage to the drug product.

Identify the indications for ABILIFY DISCMELT®.

ABILIFY DISCMELT® is an atypical antipsychotic indicated for a number of psychiatric conditions including schizophrenia, bipolar I disorder and as an adjunctive treatment for major depressive disorder

13. A modified release morphine sulfate containing dosage form (i.e., Avinza) intended for once daily dosing has been approved by FDA and sometimes results in dose dumping. How does the consumption of alcohol in the stomach cause dose dumping for Avinza? Cite your basis.

Administration of morphine sulfate (Avinza ) with alcohol, facilitates increased absorption of the drug in an alcohol-concentration related matter. This results in accelerated releases of the drug, ultimately allowing the drug to reach dangerous levels in the serum. In high serum levels Morphine Sulfate could be potentially fatal.

5. The dissolution profile provided below shows a dissolution profile for a Mesalamine drug product using a dissolution method with varying pH. Explain what is happening after 2 hours and how this is relevant in-vivo (i.e., how do conditions change in-vivo two hours after administration and what does that mean for your drug product and its performance).

After 2 hours, the drug has gone through the stomach and GI tract and has reached the ileum (The two‐hour mark on the graph represents gastric emptying time.) in order for it to be released. It has a pH dependent polymer film that does not break down until pH is over 6.8. This is why there is no absorption until 2 hours after administration. The drug is released and further absorbed over a longer period of time due to the hydrophilic and lipophilic excipients that promote extended release in the ileum and colon.

For fentanyl citrate, as shown in Figure 1 (below), explain how FENTORA® administered either between the cheek and gum (i.e., buccal pouch) or sublingually, is indistinguishable in terms of early onset of analgesia based on the physicochemical properties of fentanyl citrate (i.e., see Question 1).

Both the sublingual and buccal areas of the mouth contain similar mucosal surfaces. These surfaces are made up of a non-keratinized lining mucosa made up of superficial, intermediate, prickle pair, and basal layers. Since these two areas of the mouth are similar in composition it could be reasoned that he absorption across these surfaces will be indistinguishable. Specifically fentanyl citrate is highly lipophilic, therefore it is able to easily pass through this non-keratinized mucosal surface by the transcellular route

7. Ambien CR can be dosed at 12.5mg in men to induce AND maintain sleep; however, this may result in unwanted side effects. Describe the side effects caused by Ambien CR, as well as how you would counsel a patient who is reporting these side effects. Cite your basis.

Ambien CR can cause several side effects including: sleepiness during the day, not thinking clearly, acting strange, confused, or upset. Other side effects of Ambien CR include: sleep-walking and other activities during sleep such as eating, talking, having sex, or driving a car. However, these latter side effects are also common to Ambien. The former side effects mentioned are solely associated with Ambien CR. This is due to the controlled-release mechanism of the Ambien CR tablets. The drug is released over an extended period of time and as a result, the effects of the drug do not wane in contrast to taking Ambien. For a patient that may be reporting these side effects, we would first determine whether the patient is taking the medication properly; meaning that the medication was taken at bedtime. Additionally, it is critical that the patient gets a full night of sleep, if the patient is not able to, the effects of the drug would still be elicited because the drug is released over an extended period of time. We would also counsel the patient not to take alcohol or any other medications that induce sleep. If these symptoms continue, Ambien may be recommended. Ambien is a short-term treatment for insomnia whereas Ambien CR also treats insomnia, but its effects are longer. You can also advise the patient to reduce his administered dose, as it is also available at a 6.25mg dose strength.

2. What type of packaging would be most suitable for your selected marketed product (from Question 2)? Explain the rationale behind this packaging selection. Refer to the student handout "Packaging of Drug Products", as needed. Cite your basis.

Ambien CR is best kept in a bottle or blister package. A light resistant, well c losed container would be suitable. This will prevent light damage and maintain the stability of the preparation. The bottle can be stored at room temperature. Should be kept in child resistant packaging because it is a controlled medication.

13. . Explain why or why not an FDA approved enteric-coated dosage form would exhibit the following dissolution profile. Cite your basis using at least two references that are not Ansel's.

An FDA approved enteric-coated dosage form would not exhibit the dissolution profile described with the assumption that this dissolution profile was performed in medium simulating gastrointestinal fluid (pH changes). The dissolution of an enteric-coated dosage form is evaluated initially in acidic pH (1-2 hours in duration) and then in a phosphate buffer. The typical drug-release profile of an enteric-coated tablet is shown in the graph below. No drug is released for 1-2 hours. However, the graph shows that after about 190 minutes (3 hours) there should be 100 of drug released. Therefore, the table provided is incorrect because the drug would actually dissolve before the 6 hour mark.

13. What is the difference in a polymorph and an isomer?

An isomer is a molecule with a different molecular arrangement while a polymorph is a different crystal or packing arrangement. Both of these changes can represent a degradation or destruction of the active form of the drug. For a powder form either mutation is unlikely if the powder is stored correctly and protected from moisture.

4. 5-amino-salicylic acid, or mesalamine, is indicated to treat ulcerative colitis. Therefore, it must be delivered to the colon. Based on its indication, how does the dosage form achieve modified drug release to address ulcerative colitis? Select at least two references to cite and support your explanation.

Answer: This dosage form is a delayed-release tablet. This dosage form for this drug substance allows it to be directly targeted to the colon. Lialda is coated with a pH dependent polymer, Eudragit S and L, which breaks down at a pH of 6.8. This ensures that the drug will not be released in the acidic pH of the stomach, but rather at the terminal ileum. The ileum is where ulcerative colitis occurs, so release of the drug product there allows for Lialda to target the colitis directly. Mesalamine has systemic effects, so it is important that it is targeted towards the area of damage in the colon. Lialda also includes a hydrophilic and lipophilicmatrix for extended release.

When a patient was administered with Naproxen delayed-release tablets as a single dose along with an antacid (e.g., Tums®), the time to peak was reduced (i.e., drug was absorbed at a faster rate). Explain this phenomenon with your current understanding of modified release formulations. Cite your b

Antacids increase the pH of the stomach. If Naproxen was formulated with a pH dependent excipient that did not release its drug until a higher pH environment was available, the heightened pH would decrease drug delivery time.

ABILIFY DISCMELT® and ABILIFY® Tablets contain micronized drug, preferably less than 30 microns in average particle size. ABILIFY DISCMELT® and ABILIFY® tablets are bioequivalent to one another. Based on your understanding of the influence of particle size and surface area on the rate of dissolution of a drug substance, explain why aripiprazole in each of the products would exhibit identical dissolution profiles in water and 0.1N HCl media and be bioequivalent

As a drug is reduced in particle size, the total surface area increases. This increase in overall surface area allows for a more rapid dissolution. Abilify Discmelt utilizes super disintegrants and Abilify utilizes disintegrants. A superdisintegrant differs from a regular disintegrant because it makes up only 2-5% w/w of the dosage form. However, both forms have similar particle sizes so the two drugs exhibit bioequivalence and will therefore exhibit identical dissolution profiles.

Identify the disintegration time requirement for oral disintegrating tablets per FDA guidance document. Cite "Guidance for Industry: orally disintegrating tablets."

Based on the original product rationale and Agency from the FDA, they recommend that ODTs have an in-vitro disintegration time of approximately 30 seconds or less

7. Assume that the drug substance your team is developing is acid labile. Film coating with pH dependent polymers is the only way to make an immediate release tablet into an enteric release tablet. Do you agree? Why or why not? Cite your basis not using Ansel's.

Because our drug is acidlabile, we need to protect it from acid degradation is the stomach. Using pHdependent polymers is one way to do this, but not the only way, so we do not agree. Another method to protect our drug until it reaches the intestine is using protective coatings that are susceptible to enzymatic breakdown in the intestines. This way, the drug would would be protected in the stomach from destruction.

FENTORA® is based on the OraVescent® technology which was first described in U.S. Patent No. 6974590. This system utilizes sodium carbonate and sodium bicarbonate along with citric acid to generate an effervescent reaction that allows for rapid disintegration of the tablet and enhanced drug absorption in the buccal cavity (Eichman & Robinson, 1998). The OraVescent® system produces a dynamic pH environment where the pH fluctuates by approximately two units following administration. Explain, based on the figure below, how the dynamic pH changes influence the dissolution and permeation of fentanyl citrate. Cite your basis using at least two non-Ansel/Remington sources.

Fentora reacts with sodium carbonate and sodium bicarbonate along with citric acid to generate an effervescent reaction. Citric acid combines with bicarbonate to form carbonic acid which dissociates into carbon dioxide. This reaction allows for a decrease in pH and allows the drug to be predominately in the ionized form. This ionized form (red - orange) allows the drug to rapidly disintegrate and dissolve. Later, as there is a loss of CO2, the pH rises and allows the drug to be predominately in the unionzed form. This unionized form (blue) is more permeable to biological tissue and allows for rapid drug absorption and penetration into the membrane. This is because the unionized Fentanyl will associate more with the lipophilic molecules in the buccal mucosa and will favor transcellular penetration through the membrane.

7. Solid dosage forms, such as capsules and tablets, are best taken with a glass full of water or beverage. Attempting to swallow a tablet or capsule without water can be dangerous. Provide an example of a specific marketed drug product where this is especially important and explain why using a citation other than Ansel's textbook.

Fosamax is an FDA approved tablet that requires a full glass of water with administration of the drug. This enhances absorption of the drug and decreases the chances of esophageal irritation. This also promotes gastric emptying. Only water can be used to take this medication because other juices or liquids decrease absorption of the drug. - When administering solid dosage forms it is best to take the capsule or tablet with a full glass of water primarily because water reduces esophageal irritation, facilitates drug delivery to the stomach, and induces gastric emptying. Administration with a glass of water is also favorable because beverages other than water can alter the absorption of the drug. Fosamax (Alendronate) is an example of a drug that must be administered with a glass of water to ensure optimal drug delivery. If Fosamax is not taken standing upright with a glass of water the patient is at risk for developing esophageal ulcers

In a compounding pharmacy, what special environmental controls during manufacturing are required to work with effervescent materials in solid oral dosage forms, including those intended for administration to the oral cavity

In a compounding pharmacy, what special environmental controls during manufacturing are required to work with effervescent materials in solid oral dosage forms, including those intended for administration to the oral cavity reaction of the effervescent excipients with water to produce CO2.

FENTORA® is indicated for management of breakthrough cancer pain in cancer for patients 18 years and older. In breakthrough cancer pain, patients may experience transient exacerbations of significant and severe pain on a background of otherwise well controlled pain. These severe flare ups of pain are called breakthrough pain. This breakthrough pain has an incidence of about 40-86% as reported in various studies. In cases where the breakthrough pain episode is not relieved after 30 minutes by FENTORA®, patients may take ONLY ONE additional dose using the same strength for that episode. Why is it recommended to wait 30 minutes before taking the one additional dose? Cite your basis.

It is recommended to wait 30 minutes before taking one additional dose to ensure the patient is not being overdosed. The Tmax or time at which the max concentration occurs is at about 40 minutes. Thus, by 30 minutes you would expect to have some analgesia. At 30 minutes you know that the concentration of fentanyl citrate should be near its peak. If it is not providing analgesia at this concentration, then the patient requires a higher concentration and one additional dose can be administered

Given the dissolution profile in the figure below showing release of zolpidem tartrate from Ambien CR over time, indicate by letter (A or B) which areas are associated with the immediate release layer and the extended release layer of drug release from the bilayer tablet. Explain your rationale for your choice. Cite you basis.

Letter A represents the immediate release layer and letter B represents the extended release layer of drug release from the bilayer tablet. This is true because it shows that a high percentage of drug is quickly dissolved within half an hour (about 60% dissolved), and then it slowly gets released at a more controlled manner after that half hour. Usually, repeat action dosage forms consisting of an IR and ER layer, provide an immediate release of drug that promptly produces the desired therapeutic effect, followed by gradual release of additional amounts of drug to maintain this effect over a predetermined period

. Question 11. (5 points) Answer the following question in regards to your dosage form Mesalamine (Lialda): You must test drug release from mesalamine extended release tablet dosage form. The dissolution method provided in the Mesalamine Extended-Release Capsule USP monograph would be a good method for your dosage form. Explain why these dissolution test parameters for the capsule (ie. media used, sampling points, run time) would be suitable for Lialda.

The media used for the dissolution of the capsule is a 0.05 M pH 7.5 phosphate buffer. This is suitable because Mesalamine extended release tablet needs to reach the colon for administration, where the pH is also between 7 and 8. The sampling points used for the dissolution of the capsule are 1, 2, 4, and 8 hours. This is suitable for the extended release tablet because the tablet contains 3 different methods used to control release (i.e, hydrophobic matrix, hydrophilic matrix, and enteric coating). Using a long run time with many sample points is required to determine how long it takes for the entire dose of the drug to dissolve and be available to exert its therapeutic effect. However, this test does not test the efficacy of the enteric coating. It maintains a dissolution test at a constant pH. It would be worthwhile to test the drug at a gastric pH as well to ensure that the drug is not delivered in the stomach.

12.What type of packaging would be most suitable for your selected marketed product (from Question 2)? Explain the rationale behind this packaging selection. Refer to the student handout "Packaging of Drug Products", as needed. Cite your basis.

The most appropriate FDA approved dosage form for Mesalamine is in a tight, light resistant bottle container with child resistant closure. The tight bottle container will keep moisture from degrading the drug and the resistant closure will not allow children to have easy access to the bottle and drugs.

5. Given the figure below showing the minimum effective plasma concentration for inducing and maintaining sleep (blue line), describe the primary benefit of Ambien CR over the immediate release zolpidem tartrate form. Cite your basis.

The primary benefit of Ambien CR over the immediate-release zolpidem tartrate form is that although both drugs have a rapid initial absorption as well as a similar maximum plasma concentration values, Ambien CR has a longer minimum effective plasma concentration time, which lasts 3 hours longer than zolpidem tartrate.

Identify the route of administration of this FDA approved commercial product (from Question 2). Explain why this route of administration is suitable for this drug substance? Cite your basis.

The route of administration is oral transmucosal buccal or sublingual. This is a suitable route to obtain systemic distribution; buccal delivery allows for 50% bioavailability.

Identify the route of administration of this FDA approved commercial product (from Question 2). Explain why this route of administration is suitable for this drug substance?

The route of administration is oral. This is a suitable route to obtain systemic distribution because the dosage form must be swallowed after it disintegrates in the mouth.

Explain why this route of administration is suitable for this drug substance? Cite your basis

The route of administration is orally for gastrointestinal tract delivery. The advantages of this route of administration for this drug substance include systemic distribution of the drug.

dentify the route of administration of this FDA approved commercial product (from Question 2). Select from Table 5.4 (Ansel's 9th Edition; Chapter 5; page 161). Explain why this route of administration is suitable for this drug substance? Cite your basis.

The route of administration is to be taken orally. The advantages of this route of administration for this drug substance include luminal drug delivery. Lialda's pharmacodynamic actions occur in the colonic/rectal mucosae, which is local to where Lialda is delivered. Lialda is used to treat colonic inflammation in patients with ulcerative colitis, and it has been found that increased mucosal levels of Lialda decrease the colonic inflammation

FENTORA® is indicated for cancer patients with breakthrough pain. Xerostomia (i.e. dry mouth) is characterized by decreased salivary production. Xerostomia is commonly observed in patients undergoing radiation therapy for head and neck cancers. You are on rounds with a medical team and the physician prescribes FENTORA®. However, you are aware that the patient has xerostomia, but this fact was not discussed on rounds. What would you recommend to the physician on how to administer FENTORA® to this particular patient? Cite your basis not using Ansels or Remington.

There are multiple recommendations that can be made to the physician. One recommendation is to administer Fentora as a sublingual tablet. For patients with dry mouth that must take a sublingual tablet, water may be used to moisten the buccal mucosa before administration. In addition, Fentora is also offered as a sublingual spray. Finally, the use of artificial saliva can be utilized to improve absorption in patients with xerostomia.

Zolpidem tartrate is indicated to treat insomnia. Some patients need help with sleep onset, and in addition, they may have trouble staying asleep throughout the night. Based on its indications for sleep onset and/or sleep maintenance, how does the dosage form achieve modified drug release to address both sleep onset and sleep maintenance throughout the night? Select at least two references to cite and support your explanation.

This dosage form is a repeat action tablet. This dosage form for this drug substance provides two layers. The first layer releases the drug immediately while the second layer releases the drug over an extended period of time. Because Ambien CR is a repeat action tablet, it allows the patient to fall asleep, and because of the second layer, the patient is able to sleep throughout the night. This is because the extended release of the drug from the second layer provides a continuous supply of the drug, allowing for sleep maintenance.

Choose the MOST correct answer regarding the order of processing steps used in the pharmaceutical manufacturing process for your directly compressed film-coated tablet dosage form.

Weigh drug substance and excipients→ Blend→ Add lubricant and glidant and blend→ Compress the final blend into tablets → Coat the tablets. This is the correct sequence of processing steps because you need to weigh the substance before anything else. After weighing, you blend the ingredients to homogenize it. Lubricant and glidant is added before running the powder through the compression machine. Coating is done last because a complete tablet is necessary for coating.

term "organoleptic" refers to the properties of a product, such as its taste, odor, color and texture, that stimulate the sense organs. The organoleptic properties of a drug substance are specially important in formulation of an oral disintegrating tablet.

When formulating oral disintegrating tablets (ODTs) it is important that water-soluble excipients be incorporated to facilitate smooth and rapid dissolution of the tablet. Low-moldable sugars such as mannitol, lactose, glucose, sucrose, and erythritol are commonly used to aid in dissolution and lessen the perception of grittiness during the disintegration/dissolution process. Another technique to facilitate dissolution of ODTs includes the addition of an effervescing agent which can also aid in lessening the perception of grittiness.

13. Can hypromellose or hydroxypropyl cellulose be used as a hydrophilic gelling matrix excipient in a tablet to formulate a delayed release product that would be expected to exhibit a dissolution profile exactly like that shown in Figure 47-1 in Remington? Explain your reasons and cite your basis not using Ansel's.

hydroxypropyl cellulose would not exhibit a dissolution profile exactly like that shown in Figure 47 -1. The enteric coated dosage form in figure 47-1 is released after 2 hours and on exposure to a higher pH. The way that hydroxypropyl cellulose works is that on exposure to water or gastrointestinal fluids it will hydrate and form a viscous gel layer. Therefore, for this excipient, the release of drug is dependent on dissolution, diffusion, and erosion; it will also exhibit a more rapid release of drug. the dissolution profile shows the drug release of an enteric coated IR dosage form. Hydrophilic matrices would result in an ER drug release profile.

Zolpidem tartrate (Ambien CR)

pka of 6.2 so soluble in acidic environment