mullan pharmaceutical inc. - Medication Listings

Metformin hydrochloride tablets, USP contain the antihyperglycemic agent metformin, which is a biguanide, in the form of monohydrochloride. The chemical name of metformin hydrochloride is N,N -dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is as shown below: Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5 ∙ HCl and a molecular weight of 165.63. It is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. Metformin hydrochloride tablets, USP contain 500 mg, 850 mg or 1,000 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 662.88 mg, 779.86 mg metformin base, respectively. Each tablet contains the inactive ingredients povidone and magnesium stearate. In addition, the coating for the 500 mg, 850 mg and 1,000 mg tablets contains hypromellose and polyethylene glycol. Chemical Structure

The active ingredient in gabapentin tablets, USP is gabapentin, which has the chemical name 1-(aminomethyl) cyclohexaneacetic acid. The molecular formula of gabapentin is C 9 H 17 NO 2 and the molecular weight is 171.24. The structural formula of gabapentin is: Gabapentin is a white to off-white crystalline solid with a pK a1 of 3.7 and a pK a2 of 10.7. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is –1.25. Each gabapentin tablet, USP contains 600 mg or 800 mg of gabapentin and the following inactive ingredients: copovidone, corn starch, macrogol, magnesium stearate, polyvinyl alcohol, talc and titanium dioxide. Chemical Structure

The active ingredient in gabapentin capsules, USP is gabapentin, which has the chemical name 1-(aminomethyl) cyclohexaneacetic acid. The molecular formula of gabapentin is C 9 H 17 NO 2 and the molecular weight is 171.24. The structural formula of gabapentin is: Gabapentin is a white to off-white crystalline solid with a pK a1 of 3.7 and a pK a2 of 10.7. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is -1.25. Each gabapentin capsule, USP contains 100 mg, 300 mg, or 400 mg of gabapentin and the following inactive ingredients: corn starch, D&C red 33 (300 mg only), D&C yellow 10 (300 mg only), ferric oxide red (400 mg only), ferric oxide yellow (400 mg only), ferrosoferric oxide, gelatin, lactose monohydrate, potassium hydroxide, propylene glycol, sodium lauryl sulfate, shellac, talc, and titanium dioxide. Chemical Structure

Celecoxib capsule is a nonsteroidal anti-inflammatory drug, available as capsules containing 50 mg, 100 mg and 200 mg celecoxib for oral administration. The chemical name is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. The molecular weight is 381.38. Its molecular formula is C 17 H 14 F 3 N 3 O 2 S, and it has the following chemical structure: Celecoxib is a white to off-white powder with a pKa of 11.1 (sulfonamide moiety). Celecoxib is hydrophobic (log P is 3.5) and is practically insoluble in aqueous media at physiological pH range. The inactive ingredients in celecoxib capsules include: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate. The capsule shell contains gelatin and titanium dioxide. The imprinting ink contains the following: black iron oxide, potassium hydroxide, propylene glycol, and shellac. Chemical Structure

Amikacin Sulfate Injection, USP is semi-synthetic aminoglycoside antibiotic derived from kanamycin. It is C 22 H 43 N 5 O 13 ∙2H 2 SO 4 ∙ O -3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)- O -[6-amino-6-deoxy-α-D-glucopyranosyl-(1→6)]- N 3 -(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine sulfate (1:2) M.W. 585.61 The dosage form is supplied as a sterile, colorless to light straw colored solution for intramuscular or intravenous use. The 500 mg per 2 mL vial and 1 gram per 4 mL vial contains per each mL: 250 mg Amikacin (as the Amikacin sulfate USP), 0.66% sodium metabisulfite as an antioxidant, 2.5% sodium citrate dihydrate as a buffering agent with pH adjusted to 4.5 with sulfuric acid. Chemical Structure

Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 1-[5-[(aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl] amino]pentyl]-4-methyl-2-piperidinecarboxylic acid, monohydrate. Argatroban has 4 asymmetric carbons. One of the asymmetric carbons has an R configuration (stereoisomer Type I) and an S configuration (stereoisomer Type II). Argatroban consists of a mixture of R and S stereoisomers at a ratio of approximately 65:35. The molecular formula of argatroban is C 23 H 36 N 6 O 5 S∙H 2 O. Its molecular weight is 526.66 g/mol. The structural formula is shown below: Argatroban is a white, odorless crystalline powder that is freely soluble in glacial acetic acid, slightly soluble in ethanol, and insoluble in acetone, ethyl acetate, and ether. Argatroban Injection, USP 50 mg/50 mL (1 mg/mL) is a sterile clear, colorless to pale yellow, solution. Argatroban Injection, USP 50 mg/50 mL (1 mg/mL) is available in 50-mg (in 50-mL) single-dose vials, with blue color matte top caps. Each mL of sterile, nonpyrogenic solution contains 1 mg Argatroban. Inert ingredients (per vial): 260 mg Propylene glycol, 152 mg Dehydrated alcohol, and 450 mg Sodium Chloride. Chemical Structure

Bumetanide is a loop diuretic, available as 4-mL vials and 10-mL vials (0.25 mg/mL) for intravenous or intramuscular injection as a sterile solution. Each mL contains bumetanide 0.25 mg, sodium chloride 8.5 mg and ammonium acetate 4 mg as buffers, edetate disodium 0.1 mg and benzyl alcohol 10 mg as preservative in Water for Injection. pH adjusted to 6.8 - 7.8 with sodium hydroxide. Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder, slightly soluble in water, soluble in alkaline solutions, having the following structural formula: C 17 H 20 N 2 O 5 S Molecular weight: 364.42 Chemical Structure

Bupropion hydrochloride extended-release tablets (XL), an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin reuptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. The molecular weight is 276.2. The molecular formula is C 13 H 18 ClNO∙HCl. Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. The structural formula is: Bupropion hydrochloride extended-release tablets, USP (XL) are supplied for oral administration as 150 mg and 300 mg white to off-white extended-release tablets. Each tablet contains the labeled amount of bupropion hydrochloride, USP and the inactive ingredients: povidone, tartaric acid, glyceryl distearate, magnesium stearate, hydroxypropyl cellulose, ethylcellulose, methacrylic acid copolymer dispersion and colloidal silicon dioxide. The tablets are printed with black ink comprising of shellac glaze (modified) in SD-45, isopropyl alcohol, black iron oxide non-irradiated, n-butyl alcohol, propylene glycol and ammonium hydroxide. The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is eliminated in the feces. Meets USP Dissolution Test #4. Chemical Structure

Ganirelix Acetate Injection is a synthetic decapeptide with high antagonistic activity against naturally occurring gonadotropin-releasing hormone (GnRH). Ganirelix Acetate is derived from native GnRH with substitutions of amino acids at positions 1, 2, 3, 6, 8, and 10 to form the following molecular formula of the peptide:N-acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridyl)-D-alanyl-L-seryl-L-tyrosyl-N 9 ,N 10 -diethyl-D-homoarginyl-L-leucyl-N 9 ,N 10 -diethyl-L-homoarginyl-L-prolyl-D-alanylamide acetate. The molecular weight for Ganirelix Acetate is 1570.4 as an anhydrous free base. The structural formula is as follows: Ganirelix Acetate Ganirelix Acetate Injection is supplied as a colorless, sterile, ready-to-use, aqueous solution intended for SUBCUTANEOUS administration only. Each single dose, sterile, prefilled syringe contains 250 mcg/0.5 mL of Ganirelix Acetate, 0.1 mg glacial acetic acid, 23.5 mg mannitol and water for injection adjusted to pH 5.0 with acetic acid and/or sodium hydroxide. Chemical Structure

Labetalol hydrochloride injection is an adrenergic receptor blocking agent that has both selective alpha 1 adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance. Labetalol hydrochloride (HCl) is a racemate chemically designated as 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride, and it has the following structure: Labetalol HCl has the empirical formula C 19 H 24 N 2 O 3 ∙HCl and a molecular weight of 364.9. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol. Labetalol HCl is a white or off-white crystalline powder, soluble in water. Labetalol hydrochloride injection is a clear, colorless to light yellow, aqueous, sterile, isotonic solution for intravenous (IV) injection. It has a pH range of 3.0 to 4.5. Each mL contains 5 mg labetalol hydrochloride USP, 45 mg anhydrous dextrose, 0.10 mg edetate disodium; 0.80 mg of methylparaben and 0.10 mg of propylparaben as preservatives; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range. Chemical Structure

Milrinone lactate injection is a member of a class of bipyridine inotropic/vasodilator agents with phosphodiesterase inhibitor activity, distinct from digitalis glycosides or catecholamines. Milrinone lactate is designated chemically as 1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile lactate and has the following structure: Milrinone is an off-white to tan crystalline compound with a molecular weight of 211.2 and an empirical formula of C 12 H 9 N 3 O. It is slightly soluble in methanol, and very slightly soluble in chloroform and in water. As the lactate salt, it is stable and colorless to pale yellow in solution. Milrinone lactate is available as sterile aqueous solutions of the lactate salt of milrinone for injection or infusion intravenously. Sterile, single-dose vials: Single-dose vials of 10 and 20 mL contain in each mL milrinone lactate equivalent to 1 mg milrinone and 47 mg Dextrose, Anhydrous, USP, in Water for Injection, USP. The pH is adjusted to between 3.2 and 4.0 with lactic acid or sodium hydroxide. The total concentration of lactic acid can vary between 0.95 mg/mL and 1.29 mg/mL. These vials require preparation of dilutions prior to administration to patients intravenously. structure CLINICAL PHARMACOLOGY Milrinone lactate is a positive inotrope and vasodilator, with little chronotropic activity different in structure and mode of action from either the digitalis glycosides or catecholamines. Milrinone lactate, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle. This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle. Additional experimental evidence also indicates that milrinone lactate is not a beta-adrenergic agonist nor does it inhibit sodium-potassium adenosine triphosphatase activity as do the digitalis glycosides. Clinical studies in patients with congestive heart failure have shown that milrinone lactate produces dose-related and plasma drug concentration-related increases in the maximum rate of increase of left ventricular pressure. Studies in normal subjects have shown that milrinone lactate produces increases in the slope of the left ventricular pressure-dimension relationship, indicating a direct inotropic effect of the drug. Milrinone lactate also produces dose-related and plasma concentration-related increases in forearm blood flow in patients with congestive heart failure, indicating a direct arterial vasodilator activity of the drug. Both the inotropic and vasodilatory effects have been observed over the therapeutic range of plasma milrinone concentrations of 100 ng/mL to 300 ng/mL. In addition to increasing myocardial contractility, milrinone lactate improves diastolic function as evidenced by improvements in left ventricular diastolic relaxation. The acute administration of intravenous milrinone has also been evaluated in clinical trials in excess of 1600 patients, with chronic heart failure, heart failure associated with cardiac surgery, and heart failure associated with myocardial infarction. The total number of deaths, either on therapy or shortly thereafter (24 hours) was 15, less than 0.9%, few of which were thought to be drug-related.

Sevoflurane, USP, volatile liquid for inhalation, a nonflammable and nonexplosive liquid administered by vaporization, is a halogenated general inhalation anesthetic drug. Sevoflurane is fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether and its structural formula is: Sevoflurane, Physical Constants are: Molecular weight 200.05 Boiling point at 760 mm Hg 58.6°C Specific gravity at 20°C 1.520-1.525 Vapor pressure in mm Hg 157 mm Hg at 20°C 197 mm Hg at 25°C 317 mm Hg at 36°C Distribution Partition Coefficients at 37°C: Blood/Gas 0.63-0.69 Water/Gas 0.36 Olive Oil/Gas 47-54 Brain/Gas 1.15 Mean Component/Gas Partition Coefficients at 25°C for Polymers Used Commonly in Medical Applications: Conductive rubber 14.0 Butyl rubber 7.7 Polyvinylchloride 17.4 Polyethylene 1.3 Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13. Sevoflurane is a clear, colorless, liquid containing no additives. Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper beryllium. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform, and benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting conditions according to instructions. No discernible degradation of sevoflurane occurs in the presence of strong acids or heat. When in contact with alkaline CO 2 absorbents (e.g., Baralyme ® and to a lesser extent soda lime) within the anesthesia machine, sevoflurane can undergo degradation under certain conditions. Degradation of sevoflurane is minimal, and degradants are either undetectable or present in non-toxic amounts when used as directed with fresh absorbents. Sevoflurane degradation and subsequent degradant formation are enhanced by increasing absorbent temperature increased sevoflurane concentration, decreased fresh gas flow and desiccated CO 2 absorbents (especially with potassium hydroxide containing absorbents e.g., Baralyme). Sevoflurane alkaline degradation occurs by two pathways. The first results from the loss of hydrogen fluoride with the formation of pentafluoroisopropenyl fluoromethyl ether, (PIFE, C 4 H 2 F 6 O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether, (PMFE, C 5 H 6 F 6 O), also known as Compound B. The second pathway for degradation of sevoflurane, which occurs primarily in the presence of desiccated CO 2 absorbents, is discussed later. In the first pathway, the defluorination pathway, the production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (KOH and/or NaOH) forming an alkene (Compound A) from sevoflurane similar to formation of 2-bromo-2-chloro-1,1-difluoro ethylene (BCDFE) from halothane. Laboratory simulations have shown that the concentration of these degradants is inversely correlated with the fresh gas flow rate (See Figure 1 ). Figure 1. Fresh Gas Flow Rate versus Compound A Levels in a Circle Absorber System Since the reaction of carbon dioxide with absorbents is exothermic, the temperature increase will be determined by quantities of CO 2 absorbed, which in turn will depend on fresh gas flow in the anesthesia circle system, metabolic status of the patient, and ventilation. The relationship of temperature produced by varying levels of CO 2 and Compound A production is illustrated in the following in vitro simulation where CO 2 was added to a circle absorber system. Figure 2. Carbon Dioxide Flow versus Compound A and Maximum Temperature Compound A concentration in a circle absorber system increases as a function of increasing CO 2 absorbent temperature and composition (Baralyme producing higher levels than soda lime), increased body temperature, and increased minute ventilation, and decreasing fresh gas flow rates. It has been reported that the concentration of Compound A increases significantly with prolonged dehydration of Baralyme. Compound A exposure in patients also has been shown to rise with increased sevoflurane concentrations and duration of anesthesia. In a clinical study in which sevoflurane was administered to patients under low flow conditions for ≥ 2 hours at flow rates of 1 Liter/minute, Compound A levels were measured in an effort to determine the relationship between MAC hours and Compound A levels produced. The relationship between Compound A levels and sevoflurane exposure are shown in Figure 2a. Figure 2a. ppm∙hr versus MAC∙hr at Flow Rate of 1 L/min Compound A has been shown to be nephrotoxic in rats after exposures that have varied in duration from one to three hours. No histopathologic change was seen at a concentration of up to 270 ppm for one hour. Sporadic single cell necrosis of proximal tubule cells has been reported at a concentration of 114 ppm after a 3-hour exposure to Compound A in rats. The LC 50 reported at 1 hour is 1050-1090 ppm (male-female) and, at 3 hours, 350-490 ppm (male-female). An experiment was performed comparing sevoflurane plus 75 or 100 ppm Compound A with an active control to evaluate the potential nephrotoxicity of Compound A in non-human primates. A single 8-hour exposure of Sevoflurane in the presence of Compound A produced single-cell renal tubular degeneration and single-cell necrosis in cynomolgus monkeys. These changes are consistent with the increased urinary protein, glucose level and enzymic activity noted on days one and three on the clinical pathology evaluation. This nephrotoxicity produced by Compound A is dose and duration of exposure dependent. At a fresh gas flow rate of 1 L/min, mean maximum concentrations of Compound A in the anesthesia circuit in clinical settings are approximately 20 ppm (0.002%) with soda lime and 30 ppm (0.003%) with Baralyme in adult patients; mean maximum concentrations in pediatric patients with soda lime are about half those found in adults. The highest concentration observed in a single patient with Baralyme was 61 ppm (0.0061%) and 32 ppm (0.0032%) with soda lime. The levels of Compound A at which toxicity occurs in humans is not known. The second pathway for degradation of sevoflurane occurs primarily in the presence of desiccated CO 2 absorbents and leads to the dissociation of sevoflurane into hexafluoroisopropanol (HFIP) and formaldehyde. HFIP is inactive, non-genotoxic, rapidly glucuronidated and cleared by the liver. Formaldehyde is present during normal metabolic processes. Upon exposure to a highly desiccated absorbent, formaldehyde can further degrade into methanol and formate. Formate can contribute to the formation of carbon monoxide in the presence of high temperature that can be associated with desiccated Baralyme ® . Methanol can react with Compound A to form the methoxy addition product Compound B. Compound B can undergo further HF elimination to form Compounds C, D, and E. Sevoflurane degradants were observed in the respiratory circuit of an experimental anesthesia machine using desiccated CO 2 absorbents and maximum sevoflurane concentrations (8%) for extended periods of time (>2 hours). Concentrations of formaldehyde observed with desiccated soda lime in this experimental anesthesia respiratory circuit were consistent with levels that could potentially result in respiratory irritation. Although KOH containing CO 2 absorbents are no longer commercially available, in the laboratory experiments, exposure of sevoflurane to the desiccated KOH containing CO 2 absorbent, Baralyme, resulted in the detection of substantially greater degradant levels. Chemical Structure Figure 1 Figure 2 Figure 2a

Vecuronium Bromide for Injection is a nondepolarizing neuromuscular blocking agent of intermediate duration, chemically designated as 1-(3α,17β-Dihydroxy-2β-piperidino-5α-androstan-16β,5α-yl)-1- methylpiperidinium bromide, diacetate. The structural formula is: Its chemical formula is C 34 H 57 BrN 2 O 4 with molecular weight 637.75. Vecuronium Bromide for Injection is supplied as a sterile nonpyrogenic freeze-dried buffered cake of very fine microscopic crystalline particles for intravenous injection only. Each vial contains 10 mg or 20 mg of vecuronium bromide, USP. In addition, each 10 mg vial contains 20.75 mg citric acid anhydrous, 16.25 mg dibasic sodium phosphate anhydrous, 97 mg mannitol (to adjust tonicity), sodium hydroxide and/or phosphoric acid to buffer and adjust to a pH range of 3.5 to 4.5. Each 20 mg vial contains 41.5 mg citric acid anhydrous, 32.5 mg dibasic sodium phosphate anhydrous, 194 mg mannitol (to adjust tonicity), sodium hydroxide and/or phosphoric acid to buffer and adjust to a pH range of 3.5 to 4.5. Chemical Structure