By F. Masil. University of Texas at San Antonio.

Diluents Diluents are inert substances added to the active ingredient to bulk up the formulation purchase 45mg actos fast delivery, in order to make a reasonably sized tablet 45mg actos mastercard, or to fill a capsule. Carbohydrates are commonly used, such as lactose, dextrose, sucrose, and microcrystalline cellulose. Hydrophilic diluents promote rapid tablet disintegration and therefore liberate the drug quickly from the dosage form, which promotes absorption. Some diluents dissolve very slowly and therefore release of the drug occurs by tablet erosion, rather than tablet disintegration. However, a hydrophobic diluent impedes penetration of gastrointestinal fluids, so that dissolution of drug occurs only from the surface of the plug-shaped mass. Binders (adhesives) In tableting, binders are used to bind powders together in the wet granulation process. These agents coat the drug particles and therefore the rate of binder dissolution can determine the drug release rate. Disintegrants The purpose of a disintegrant is to cause the tablet to disintegrate rapidly, so as to generate an increased surface area which facilitates rapid drug dissolution. An alternative mechanism involves capillary action, in which liquid is drawn up through capillary pathways within the tablet and ruptures the interparticulate bonds, which serves to break the tablet apart. Obviously, disintegrants with high swelling and hydrating capacities promote rapid dissolution and thus a high bioavailability. Lubricants Lubricants act by interposing an intermediate layer between the tablet constituents and the die wall, to prevent adherence of the granules to the punch faces and dies. The most effective lubricants, such as magnesium stearate, are very hydrophobic and can also prevent wetting of powders and hence retard dissolution (Figure 6. Newer technologies may also incorporate additives such as enzyme inhibitors, to prevent premature degradation of enzymatically labile drugs. For example, the inclusion of trypsin inhibitors, such as soyabean trypsin inhibitor and aprotinin, have been shown to be effective in enhancing the effect of insulin in rats. Penetration enhancers may also be included to facilitate the uptake of poorly absorbed moieies. A brief overview of both the advantages and disadvantages of oral drug delivery is given below. Large surface area The total surface area of the small intestine in humans is approximately 200 m , which represents a large2 effective surface area for drug absorption. Rich blood supply The highly vascular surface of the gastrointestinal mucosa ensures rapid absorption and onset of action, as well as the maintenance of sink conditions. Zero-order controlled release Oral drug delivery offers the potential to achieve zero-order controlled release. Commercial advantages The cost of oral therapy is generally much lower in comparison to parenteral and other routes of delivery. In addition, a number of patient variables (gender, race, age, and disease state) can also drastically alter the absorption of orally administered drugs. As so many variables influence the availability of the drug at the target site, there is great potential amongst orally administered drugs for bioinequivalence. Adverse reactions Locally irritating or sensitizing drugs must be used with caution in this route. For example, some drugs are gastro-toxic, causing damage to the mucosal lining of the stomach. Adverse environmental effects The nature of the gastrointestinal environment also limits the types of drugs that may be administered via this route. Adverse environmental effects include: High metabolic activity The high metabolic activity creates a formidable biochemical barrier to the delivery of enzymatically labile drugs. In particular, the oral bioavailability of therapeutic peptides and proteins is very low (typically<1%). Extreme of pH Some drugs are acid-labile and are degraded by the highly acidic conditions of the stomach. Delays in gastric emptying rates can prolong the residence time of drugs in the stomach, increasing the potential for acid-mediated degradation. Intestinal motility Intestinal motility can severely constrain the contact time of a drug moiety with the absorbing surface. Mucus barrier Drug diffusion may be limited by the physical barrier of the mucus layer and the binding of drugs to mucus. P-glycoprotein efflux pump By restricting the transcellular flux of some molecules, this pump serves as further barrier to drug absorption. Impermeable epithelium 152 The organization and architecture of the gastrointestinal epithelium provides a substantial physical barrier to the absorption of large, hydrophilic molecules such as therapeutic peptides, proteins and oligonucleotides. For example, although insulin was commercially introduced in 1923, despite intensive research efforts directed towards attaining its oral delivery, all approaches have proven unsuccessful, and an oral form of insulin is as yet not commercially available. When rapid, efficient absorption of drugs is desired, aqueous solutions represent the oral dosage form of choice. Drugs in suspension are also readily absorbed because, as described above, the large available surface area of the dispersed solid facilitates rapid dissolution and absorption.

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Transfer into storage vessel and set temperature filter sieves; set the temperature to 60°C discount 45 mg actos with mastercard. Acetaminophen Suppositories Bill of Materials Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 500 purchase 30mg actos amex. Load item 1 and mix at 10 rpm and homogenize at speed I for 10 minutes maintaining the tem- 1. Load item 2 in the fat-melting vessel and heat perature of 50°–55°C under vacuum as above to 60°C. Transfer into storage vessel and set temperature filter sieves; set the temperature to 60°C. Acetylsalicylic Acid Suppositories Bill of Materials Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 100. Continue mixing and cooling and pour into molds at 35°C that were previously chilled to 1. Each gram of ointment contains The corticosteroids constitute a class of primarily syn- 0. Homogenize at high speed for 15 minutes at 10–12 rpm, manual mode, and temperature a temperature of 45°C with continuous mix- 70° ± 2°C. Cool down to 25°–30°C with continuous in a water bath with the help of homogenizer. Aloe Vera Gel Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 4. Formulations of Semisolid Drugs 101 Alum Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 4. While stirring, the cream is cooled to about olin alcohol, octyldodecanol, and white petro- 30°C, and its weight is supplemented with puri- latum weighed and mixed in the ratio defined fied water. Alum and item 7 are dissolved in water at room then filled into an electrolyte-resistant storage temperature, and then the solution is heated to bottle. Aminacrine Hydrochloride Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Cool down to 45°C and add perfume, continue suitable mixing vessel; heat to 60°C and mix to mix to cool down to room temperature. Prepare slurry of item 1 in the balance of item 6 and add to step 1 slowly at 60°C under con- stant stirring. The chemical name of anthralin of glyceryl monolaurate, glyceryl monomyristate, citric is 1,8-dihydroxy-9-anthrone. Formulations of Semisolid Drugs 103 Antifungal Topical Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 39. Arginine and Oleoresin Capsicum Cream Active ingredients: L-arginine and oleoresin capsicum. In another vessel, prepare a solution of items 13–16 heated to 75°C with stirring. Atropine Opthalmic Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 1. In a separate vessel, dissolve item 1 in 200 mL of water for injection and add to step 1 under 1. Formulations of Semisolid Drugs 105 Azelaic Acid Cream and Gel Azelaic acid cream 20% contains azelaic acid, a naturally in usual concentrations in 60–70 parts of water. Chemical name: 1,7-heptanedi- polysorbate 80 is added and homogenized while being carboxylic acid. The solution that is produced ents: cetearyl octanoate, glycerin, glyceryl stearate, cet- is stirred into the preemulsion and homogenized. Sodium hydroxide is used to neturalize the car- Benzoic acid is present as a preservative. It has a potency of not less than 6000 polymyxin of bacitracin, a mixture of related cyclic polypeptides B units per milligram, calculated on an anhydrous basis. It has a potency of not less than 40 bacitracin units equal to 10,000 polymyxin B units; inactives: white pet- per milligram. After cooling the oleaginous phase to about 55°C, the triacetin solution is added to the ole- 1. Mixing should be pylene glycol stearate are melted together by of sufficient intensity to disperse the triacetin heating to 75°–85°C, and mixed, thus creating finely and uniformly. Base Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 10. After cooling the oleaginous phase to about 45°C, the triacetin is added to the oleaginous phase while mixing. Mixing should be of suf- ficient intensity to disperse the triacetin finely and uniformly. Formulations of Semisolid Drugs 107 Base Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 5. To make the oleaginous phase, white petrola- perse the triacetin finely and uniformly. Mixing is continued while cooling the ointment crystalline wax are melted at 75°–85°C.

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While they enhance con- tractility and lower vascular resistance purchase actos 15mg fast delivery, they also have been associated with sudden death likely due to increasing meta- bolic demand generic actos 45 mg mastercard. Amyl Nitrite Class of drug: Antianginal, nitrate vasodilator, antidote to cyanide poisoning. Mechanism of action: As antianginal agent, reduces peripheral resistance (arterial and venous) by vasodilation; decreases left ventricular pressure. As antidote for cyanide poisoning, pro- duces methemoglobin which binds and inactivates cyanide. If signs of poisoning reappear, administer 50% of initial dose of sodium nitrite and sodium thiosufate. Advice to patient: Advise patient that if pain is not relieved after 3 doses, call paramedics or to emergency room immediately. Mechanism of action: Competitive blocker of β-adrenergic receptors in heart and blood vessels. Adjustment of dosage • Kidney disease: creatinine clearance 15–35 mL/min: 50 mg/d; creatinine clearance <15 mL/min : 25 mg/d. If necessary to dis- continue, taper as follows: Reduce dose by 25–50% and reassess after 1–2 weeks. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Sit at the edge of the bed for several minutes before standing, and lie down if feeling faint or dizzy. Clinically important drug interactions • Drugs that increase effects/toxicity of β blockers: reserpine, bretylium, calcium channel blockers. If hypotension occurs despite correction of bradycardia, administer vasopressor (norephinephrine, dopamine, or dobutamine). Stop therapy and administer large doses of β-adrenergic bronchodilator, eg, albuterol, terbutaline, or aminophylline. Some advocate discontinuing the drug 48 hours before surgery; others recommend withdrawal for a considerably longer time. These drugs are also first choice for chronic stable angina, used in conjunction with nitroglycerin. Contraindications: Hypersensitivity to statins, active liver dis- ease or unexplained persistent elevations of serum transaminase, pregnancy, lactation. Warnings/precautions • Use with caution in patients with the following conditions: renal insufficiency, history of liver disease, alcohol abusers. Values should be obtained prior to and periodically after treat- ment begins to ascertain drug efficacy. It may be advisable to take a liver biopsy if transaminase elevation persists after drug is discontinued. Mechanism of action: Blocks nicotinic acetylcholine receptors at neuromuscular junction resulting in skeletal muscle relax- ation and paralysis. Editorial comments • This drug is not listed in Physician’s Desk Reference, 54th edi- tion, 2000. Mechanism of action: Blocks acetylcholine effects at mus- carinic receptors throughout the body. Adverse reactions • Common: Dry mouth, blurred vision (decreased accommodation), drowsiness, tachycardia, urinary hesitancy, dry skin, constipation. Parameters to monitor • Signs and symptoms of severe toxicity: tachycardia, supraven- tricular arrythmias, delirium, seizures, agitation, hyperthermia. Discontinue physostigmine if patient experiences dizziness, palpitations, rapid pulse. Editorial comments • This drug is not listed in the Physician’s Desk Reference, 54th edition, 2000. Mechanism of action: Inhibits phagocytosis, stabilizes lysoso- mal membranes, decreases rheumatoid factor levels. Related compounds considered compatible with breast- feeding by the American Academy of Pediatrics. Contraindications: History of gold-associated disorders such as necrotizing enterocolitis, exfoliative dermatitis, pulmonary fibro- sis, bone marrow insufficiency, drugs known to cause blood dyscrasias (antimalarials, pyrazolones, immunosuppressants). Warnings/precautions • Use with caution in patients with the following conditions: hepatic, renal, inflammatory bowel disease. Advice to patient: Use sunscreen and protective clothing to avoid photosensitivity reactions. Adverse reactions • Common: diarrhea (47%), abdominal cramping (14%), nausea, vomiting, rash (24%), pruritus (17%), stomatitis. Clinically important drug interactions • Drugs that increase effects/toxicity of auranofin: penicillamine, immunosuppressants, cytotoxic drugs. Editorial comments: This drug is not listed in the Physician’s Desk Reference, 54th edition, 2000. Editorial comments • Usually available in combination with other agents, including pseudoephedrine, phenylephrine, and phenylpropanolamine. Warnings and precautions, side effects, etc, of other ingredients should be kept in mind when prescribing.

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