Picture from Leon Shargel & Andrew B.C. Yu. Applied Biopharmaceutics &
Pharmacokinetics. 4th Edn. 1999. Appleton & Lange, Stamford, CT. EXTENSION
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CHAPTER 10.
ONCE-A-DAY ORAL DOSAGE FORMS
ONCE-A-DAY ORAL DOSAGE FORMS
1. DRUGS BECOMING ACTIVE METABOLITE WITH LONG HALF-LIVES
2. DRUGS WITH SHORT HALF-LIVES
CLARITIN
I. ORAL CONTROLLED RELEASE DOSAGE FORMS
PRILOSEC (OMEPRAZOLE) HALF-LIFE OF 0.5-1 HOUR
LORATADINE: HALF-LIFE OF 8 HOURS DESCARBOETHOXYLORATADINE: 28 H
INHIBITION OF H+/K+ ATPase ENZYME SYSTEM LASTS 24-72 HOURS
CLARITIN-D 24 HOUR EXTENDED RELEASE IS FOR PSEUDOEPHEDRINE
Factors to consider in designing drug delivery systems
Drug Property
Drug Property
Molecular Weight Stability Solubility
Molecular Weight Stability Solubility
Administration Route
Biocompatibility
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Optimum Dosage Form
Targeting
Delivery Vehicle
Targeting
Delivery Vehicle
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Release Mechanism
Release Mechanism
Continuous delivery Modulated delivery
Continuous delivery Modulated delivery
Duration of Release
Drug Property
ORAL DRUG DELIVERY MOST PREFERRED ROUTE OF DELIVERY Administration Route
Biocompatibility
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Oral
Optimum Dosage Form Targeting
Delivery Vehicle
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue Release Mechanism
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Optimum Dosage Form
Molecular Weight Stability Solubility
Administration Route
Biocompatibility
LIMITING FACTORS FOR ORAL CONTROLLED RELEASE DOSAGE FORMS 1. RELATIVELY SHORT GASTRIC EMPTYING TIME AND INTESTINAL TRANSIT TIME
Swallowable
Continuous delivery Modulated delivery Duration of Release
Page 1
Duration of Release
Oral
Drug Property
Drug Property
Molecular Weight Stability Solubility
Molecular Weight Stability Solubility
Administration Route
Biocompatibility
Administration Route
Biocompatibility
Oral
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
LIMITING FACTORS FOR ORAL CONTROLLED RELEASE DOSAGE FORMS Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Optimum Dosage Form Delivery Vehicle
Targeting
Delivery Vehicle
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Swallowable
Release Mechanism
Gastric retention
Continuous delivery Modulated delivery
1. RELATIVELY SHORT GASTRIC EMPTYING TIME AND INTESTINAL TRANSIT TIME 2. NON-UNIFORM ABSORPTION ABILITIES OF DIFFERENT SEGMENTS OF THE GI TRACT
Optimum Dosage Form
Targeting
Duration of Release
Oral
Swallowable
Release Mechanism Continuous delivery Modulated delivery
< 1 day
Duration of Release
< 1 day
Esophagus Gastro-esophageal junction
Fundus
Pyloric sphincter
Body
Stomach Antrum
Duodenum
Transverse colon
Small intestine
Jejunum
Ascending colon
Descending colon
Large intestine
Ileum
Cecum Sigmoid colon Rectum
Drug Property
LIMITING FACTORS FOR ORAL CONTROLLED RELEASE DOSAGE FORMS
2. NON-UNIFORM ABSORPTION ABILITIES OF DIFFERENT SEGMENTS OF THE GI TRACT 3. PRESYSTEMIC CLEARANCE
Plasma mettoprolol (ng/ml)
1. RELATIVELY SHORT GASTRIC EMPTYING TIME AND INTESTINAL TRANSIT TIME
Molecular Weight Stability Solubility
160 140
Intragastric infusion
120
Oros
Administration Route
Biocompatibility
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
100 80
Oral
Optimum Dosage Form
60 40 20 0 0
5
10
15
20
Time (h)
25
30
Targeting
Delivery Vehicle
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
35
Gastric retention Colon targeting
Release Mechanism
Duration of Release
Page 2
Swallowable
Continuous delivery Modulated delivery
< 1 day
Drug Property
Most polymers
Drug Property
Molecular Weight Stability Solubility
Most polymers Administration Route
Biocompatibility
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Molecular Weight Stability Solubility
Administration Route
Biocompatibility
Oral
High Mol.Wt.? Permeability
Oral, Pulmonary, Transdermal, Implantable, Parenteral
Mutual effects between body and dosage form
Optimum Dosage Form
Optimum Dosage Form
Targeting
Delivery Vehicle
Targeting
Delivery Vehicle
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Organ Tissue Cell Cell components
Polymer Size & Shape Cell Tissue
Gastric retention Colon targeting
Swallowable
Release Mechanism Continuous delivery Modulated delivery Duration of Release
Oral
Gastric retention Colon targeting
< 1 day
LIMITING FACTORS FOR ORAL CONTROLLED RELEASE DOSAGE FORMS
Swallowable
Release Mechanism Continuous delivery Modulated delivery Duration of Release
LIMITING FACTORS FOR ORAL CONTROLLED RELEASE DOSAGE FORMS 1. RELATIVELY SHORT GASTRIC EMPTYING TIME AND INTESTINAL TRANSIT TIME 2. NON-UNIFORM ABSORPTION ABILITIES OF DIFFERENT SEGMENTS OF THE GI TRACT 3. PRESYSTEMIC CLEARANCE 4. POOR ABSORPTION OF PEPTIDES AND PROTEIN DRUGS
< 1 day
Oral Drug Delivery Technologies
EXTENSION OF GASTRIC RETENTION TIME A NUMBER OF APPROACHES
1. RELATIVELY SHORT GASTRIC EMPTYING TIME AND INTESTINAL TRANSIT TIME
Gastric retention devices
2. NON-UNIFORM ABSORPTION ABILITIES OF DIFFERENT SEGMENTS OF THE GI TRACT
EXTENSION OF INTESTINAL TRANSIT TIME RELATIVELY MORE DIFFICULT
3. PRESYSTEMIC CLEARANCE FOCUS ON DEVELOPMENT OF GASTRIC RETENTION DEVICES
4. POOR ABSORPTION OF PEPTIDES AND PROTEIN DRUGS 5. POOR IN VITRO-IN VIVO CORRELATION
Picture from Leon Shargel & Andrew B.C. Yu Applied Biopharmaceutics & Pharmacokinetics. 4th Edn. 1999 Appleton & Lange, Stamford, CT
METHODS OF EXTENDING GASTRIC RETENTION TIME
INTRAGASTRIC FLOATING SYSTEMS (LOW DENSITY SYSTEMS)
HYDRODYNAMICALLY BALANCED INTRAGASTRIC DELIVERY SYSTEMS
1. INTRAGASTRIC FLOATING SYSTEMS Gelatinous barrier
(LOW DENSITY SYSTEMS) 2 HIGH DENSITY DOSAGE FORMS 2.
A
B
3. MUCOADHESIVE DOSAGE FORMS
Drug diffusion
HBS Gastric fluid
4. UNFOLDABLE, EXTENDIBLE, OR EXPANDABLE SYSTEMS
Dry mass d
