Chapter 20: Dosage forms, Slides of Computer science

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NOVEL

DOSAGE

FORMS

AND DRUG

DELIVERY

TECHNOLO

GIES

CHAPTE

R

New drug delivery systems can

provide improved or unique

clinical benefit, such as:

a) Improvement of the patient’s compliance b) Improved outcomes c) Reduction of adverse effects d) Improvement of the patient’s acceptance of the treatment e) Avoidance of costly interventions such as laboratory services f) Allowing the patients to receive medication as outpatients g) A reduction in the overall use of medicinal resources

Novel drug delivery systems can

include:

Physical mechanisms – also referred to as controlled drug delivery systems, include osmosis, diffusion, erosion, dissolution and electrotransport Biochemical mechanisms – include monoclonal antibodies, gene therapy and vector systems, polymer drug abducts, and liposomes.

Therapeutic benefits

• (^) Optimization of the duration of action of the drug
• (^) Decreasing dosage frequency
• (^) Controlling the site of release
• (^) Maintaining constant drug levels.

Safety benefits

• (^) Reducing adverse effects
• Decreasing the number of concomitant medications a patient must take
• (^) Decreasing the need for interventions
• Reducing the number of emergency department visits.

Economic benefits

• (^) Simplifying administration

regimens

• (^) Enhancing the patient’s

compliance

• (^) An overall reduction of health

care costs

T O P I C A L A D M I N I S T R A T I O N Phonophoresis Iontophoresis 01 02

T O P I C A L A D M I N I S T R A T I O N Iontophoresis

• IP is an electrochemical method that enhances the transport of some solute molecules by creating a potential gradient through the skin with an applied electrical current or voltage.
• (^) Negative ions are delivered by the cathode and positive ions by the anode. A typical IP device consists of a Battery Microprocessor controller Drug reservoir Electrodes Advantages of IP includes: a) Control of the delivery rates by variations of current density, pulsed voltage, drug concentration, and ionic strength b) Eliminating gastrointestinal incompatibility, erratic absorption, and first- pass metabolism c) Reducing side effects and variation among patients d) Avoiding the risks of infection, inflammation, and fibrosis associated with continuous injection or infusion e) Enhancing compliance with a convenient and non-invasive therapeutic regimen. Main Disadvantage of IP is skin irritation at high current densities.

T O P I C A L A D M I N I S T R A T I O N Iontophoresis Variables affecting IP include:

• Aspects of the current
• The physicochemical properties of the drug
• Formulation factors
  • Biologic factors,
  • Electroendosmotic flow Current can be: Direct, alternate, or pulsed and can have various waveforms, including square, sinusoidal, triangular, and trapezoidal. Physicochemical variables include the charge, size, structure, and lipophilicity of the drug. The drug should be:
• Water soluble
• (^) Low dose
• (^) Ionizable with a high charge density
• (^) Smaller molecules Formulation factors – include drug concentration, pH, ionic strength, and viscosity.
• Increasing drug concentration usually results in greater drug delivery to a certain degree.
• Buffer ions in a formula will compete with the drug for the delivery current, decreasing the quantity of drug delivered, especially because buffer ions are generally smaller and more mobile than the larger active drug.
• The pH of solutions can be adjusted and maintained by larger molecules, such as ethanolamine: ethanolamine HCl rather than the smaller hydrochloric acid and sodium hydroxide.
• (^) An increase in ionic strength of the system will also increase the competition for the available current.

T O P I C A L A D M I N I S T R A T I O N Iontophoresis

• Biologic factors – pertain to the skin to which the electrodes are applied, its thickness, permeability, presence of pores.
• (^) Electroendosmotic flow results when a voltage difference is applied across a charged porous membrane, resulting in a bulk fluid flow in the same direction as the flow of counter ions.
• (^) The next generation of IP patch may also include an electronic record of the date, time, and quantity of each dose delivered, providing information for determining patient compliance. Also, units may soon be capable of reverse IP that serves to collect a sample noninvasively and determine the analyte levels in the body with feedback mechanisms for dosing.
• (^) It may include IP patches capable of sampling and testing (e.g., glucose levels) and adjusting the delivery rate of a drug (e.g., insulin), all in the same IP system. Reverse IP can be used to extract chemicals or drugs from the body for testing.
• (^) An IP system called Numby Stuff (IOMED) is used to achieve local anesthesia of the skin and is promoted as a painless, needleless system.
• (^) IP has been studied to enhance ungula penetration for the treatment of fungal infections in the nails.

Tapes

• The active drug is generally in the dry state. The adhesive layer is designed to hold the tape securely in place without the need for additional bandaging. Unlike transdermal patches, tapes are not designed to control the release rate of the drug.
• (^) The use of an occlusive dressing with the tape enhances the rate and extent of delivery of the drug to deeper layers of the skin and may result in greater systemic absorption of the drug.
• (^) Tapes should be stored in tight containers and protected from light and moisture. - (^) A tape is a dosage form suitable for delivering active pharmaceutical ingredients to the skin. It consists of the drug(s) impregnated into a durable yet flexible woven fabric or extruded synthetic material that is coated with an adhesive agent.  (^) They should be labeled “For External Use Only.”  (^) To use, one cuts a patch slightly larger than the area that will be treated. The backing paper is removed from the adhesive side and the tape applied to the skin.  (^) To ensure optimal adhesion, the tape should not be applied to folds in the skin.  (^) To minimize systemic absorption and to ensure good adhesion, tapes should be

FILMS MUCOADHESIVE SYSTEM Is a thin, flexible sheet of material. They are prepared by mixing the polymer with the drug, sweetener, and flavor and casting, forming, drying, and packaging.

• (^) The Striant mucoadhesive testosterone buccal system is designed to adhere to the gum or inner cheek to provide a controlled and sustained release of testosterone through the buccal mucosa
• (^) Using a Striant system twice daily, morning and evening, provides continuous systemic delivery of testosterone to the patient. Each Striant buccal system contains 30 mg of testosterone, along with the inactive ingredients such as anhydrous lactose, Carbomer 934P, hypromellose, magnesium stearate, lactose monohydrate, polycarbophil, colloidal silicon dioxide, starch, and talc.
• (^) When used as directed in hypogonadal males, the circulating testosterone levels should approximate the physiologic levels in healthy men at 300 to 1,050 ng/dL.
• (^) When applied, Striant begins hydrating, and testosterone is absorbed through the gum and cheek surfaces that are in contact with it. Venous drainage from the mouth into the superior vena cava circumvents first- pass (hepatic) metabolism.

Medicated Gums Is a semisolid confection that is designed to be chewed rather than swallowed.

• Medicated gums release their active ingredient(s) into the saliva and can deliver therapeutic agents for both local action or for systemic absorption.
• (^) They are formulated from insoluble synthetic gum bases, such as polyisoprene , polyisobutylene, isobutylene–isoprene copolymer, styrene butadiene rubber, polyvinyl acetate, polyethylene, ester gus, or polyterpenes.
• Softening agents, or plasticizers such as propylene glycol, glycerin, oleic acid, or vegetable oils, are added to maintain pliability and aid in the incorporation of the active and inactive ingredients, including sweeteners and flavoring agents.
• (^) Some medicated gums are coated with magnesium stearate to reduce tackiness and improve handling during packaging.
• (^) With the Alzet pump, the drug reservoir is a liquid solution inside an impermeable colapsible polyester bag coated with a layer of an osmotically active salt.
• As the salt dissolves, it creates an osmotic pressure gradient, and the drug compartment is reduced in volume, forcing the drug solution out. The delivery rate can be changed by changing the drug concentration.

VAGINAL ADMINISTRATION  (^) Intravaginal Drug Delivery System  (^) Intrauterine Progesterone Drug Delivery System  (^) Dinoprostone Vaginal Insert  (^) Estring  (^) Crinone Gel Intravagina l Drug Delivery System

• (^) System Vaginal administration of drugs, especially hormones, has several advantages, including: Self-insertion and removal Continuous drug administration at an effective dose level Good patient compliance.
• (^) In a polymeric vaginal drug delivery system, such as a resilient medicated vaginal ring, the drug may be uniformly distributed throughout the polymeric matrix. Upon administration and when in contact with vaginal fluids, the drug will slowly dissolve and migrate out of the device. Drug inside the device will diffuse toward the surface along a concentration gradient, resulting in a long- acting drug delivery system.
• (^) Mirena (levonorgestrel-releasing intrauterine system) consists of a T-shaped polyethylene frame with a steroid reservoir (hormone elastomer core) around the vertical stem. It is designed to prevent pregnancy for up to 5 years.

VAGINAL ADMINISTRATION  (^) Intravaginal Drug Delivery System  (^) Intrauterine Progesterone Drug Delivery System  (^) Dinoprostone Vaginal Insert  (^) Estring  (^) Crinone Gel Intrauterin e Progesteron e Drug Delivery System

• The Progestasert System slowly releases an average of 60 mg of progesterone per day for 1 year after insertion.
• (^) The continuous release of progesterone into the uterine cavity provides local rather than systemic action. Two hypotheses for the contraceptive action have been offered: Progesterone-induced inhibition of sperm capacity for survival Alteration of the uterine milieu to prevent nidation.
• (^) The intrauterine device contains 38 mg of progesterone. The intrauterine device is replaced annually for the maintenance of contraception.
• (^) The Progestasert provides contraception without the need for daily self-medication and has the advantages of a. Using a natural hormone; b. Containing no estrogens; c. Using a T-shaped delivery device to ensure comfort, safety, and retention d. Confining the hormonal action to the uterus.
• (^) The device contains the progesterone suspended in silicone oil; barium sulfate is added to make it radiopaque. The ethylene vinyl acetate (EVA) membrane surrounding the drug core

VAGINAL ADMINISTRATION  (^) Intravaginal Drug Delivery System  (^) Intrauterine Progesterone Drug Delivery System  (^) Dinoprostone Vaginal Insert  (^) Estring  (^) Crinone Gel Estring

• (^) A unique method of administering estradiol is through the use of the estradiol vaginal ring (Estring, Pharmacia Corp., A Division of Pfizer)
• (^) The core of the ring contains a reservoir of estradiol.
• (^) The ring is inserted into the upper third of the vaginal vault and is worn continuously for the treatment of urogenital symptoms associated with postmenopausal atrophy of the vagina.

VAGINAL ADMINISTRATION  (^) Intravaginal Drug Delivery System  (^) Intrauterine Progesterone Drug Delivery System  (^) Dinoprostone Vaginal Insert  (^) Estring  (^) Crinone Gel Crinone Gel

• (^) Another type of vaginal product with extended action is the bioadhesive vaginal gel Crinone Gel (Wyeth-Ayerst) , which contains micronized progesterone and the polymer polycarbophil in an oil-in-water emulsion system.
• (^) The polymer, which is insoluble in water, swells within the vagina and forms a bioadhesive gel coating on the walls of the vagina.