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International Journal of Pharma Professional's Volume 2, Issue4,October- 2011 Available Online at www.ijppronline.in International Journal Of Pharma Professional’s Research Review Article PHARMACOKINETIC SOLUBILITY AND DISSOLUTION PROFILE OF ANTI-CANCER DRUGS ISSN NO:0976-6723 Achhrish goel*1 , shivani saini2 , Vicky chowdhry3, syed azeem haider1, robin kumar singh1 1.Teerthankar mahaveer college of pharmacy,Teerthankar mahaveer university,Moradabad 2.Guru Jambheshwar University of Science and Technology, Hisar, Haryana 3.Shoolini university,solan Abstract Pharmacokinetic data, Solubility Profile and Dissolution profile of drugs are the basic requirement of any researcher, for selecting an appropriate drug for any kind of formulation development. To get such data of all drugs of any category at one place is very difficult task; we by our review article have tried to give all such data of anticancer drugs at one place. Keywords: - Solubility profile, pharmacokinetic parameters, Dissolution profile, Anticancer drugs. Introduction B. Drugs altering hormonal milieu Classification: - 1. Glucocorticoids- prednisolone and others A. Drugs acting directly on cells (cytotoxic 2. Estrogens-fosfestrol, ethylinylestradiol drugs) 3. Selective estrogen receptor modulators- tamoxifen, 1.Alkylating agent- Nitrogen mustards:- toremifene. mechlorethamine cyclophosphamide, ifosamide, 4. Selective estrogen receptor down regulators- fulvestrant chlorabucil, melphalanethylenimine- thio-TEPA, 5. Aromatase inhibitor- Letrozole, anastrozole, exemestane alkyl sulfonate- busulfan, nitrosoureas- carmustine 6. Antiandrogen- flutamide, bicultamide (BCNU), lomustine (CCNU), triazine- dacarbazine 7.5-alpha reductase inhibitor - finasterride, dutasteride (DTIC) 8. GnRHanalogues- nafareline, triporelin 2. Antimetabolites: Folate antagonist- methotrexate 9. Progestins-hydroxyprogesterone acetate.(1) (Mtx) Purineantagonist- 6-mercaptopurine, 6-thioguanine, Mechlorethamine[2] azathioprine, fludarabine. Pyrimidine antagonist- 5-flurouracil, cytarabine 3. Vinca alkaloid- vincristine, vinblastine 4. Taxane- paclitaxel, docetaxel 5. Epipodophyllo toxin-etoposide. 6. Camptothecin analogues- topotecan, irinotecan Systematic (IUPAC) name: - 2-chloro-N-(2-chloroethyl)- 7.Antibiotics- actinomycin D, doxorubicin, N-methyl-ethanamine daunorubicin, mitoxantrone, belomycins, mitomycin C. Chemical Data: - 8. Miscellaneous-hydroxyurea, procarbazine, L- Molecular formula: - C5H11Cl2N. [3] asparginase, cisplatin, carboplatin, imatinib. Molecular Weight: - 172.053 g/mol. [4] Correspondence Address: Boiling Point: - 110.3°C at 760 mmHg. [5] Achhrish goel Melting point: - 108-111°C. [6] Teerthankar mahaveer college of pharmacy Description : It is a light yellow brown, crystalline, Teerthankar mahaveer university,moradabad hygroscopic powder. [7] Phone no: +91-9412367363 Solubility profile: - very soluble in water and also soluble in E-mail- [email protected] alcohol. [8] 418 Volume 2, Issue4,October- 2011 Mechanism of Action: - Alkylating agents work by Solubility profile: - Soluble in water and in alcohol. three different mechanisms: 1) attachment of alkyl [20][USP] groups to DNA bases, resulting in the DNA being Solubility profile: - Free soluble in ethanol (95%), soluble fragmented by repair enzymes in their attempts to in water, slightly soluble in ether. [21][IP] replace the alkylated bases, preventing DNA Mechanism of action: - Alkylating agents work by three synthesis and RNA transcription from the affected different mechanisms: 1) attachment of alkyl groups to DNA DNA, 2) DNA damage via the formation of cross- bases, resulting in the DNA being fragmented by repair links (bonds between atoms in the DNA) which enzymes in their attempts to replace the alkylated bases, prevents DNA from being separated for synthesis or preventing DNA synthesis and RNA transcription from the transcription, and 3) the induction of mispairing of affected DNA, 2) DNA damage via the formation of cross- the nucleotides leading to mutations. links (bonds between atoms in the DNA) which prevents Mechlorethamine is cell cycle phase-nonspecific. [9] DNA from being separated for synthesis or transcription, and Pharmacokinetic data: - 3) the induction of mispairing of the nucleotides leading to Bioavailability: - variable, with 20-50 per cent mutations. [22] being excreted in the stool. [10] Pharmacokinetic data Metabolism: - Rapid hydrolysis and Bioavailability: - >75% (oral) demethylation, possibly in plasma Protein binding: - >60% Half-life: - < 1 minute Metabolism: - Hepatic Excretion: - Urine (50% as metabolites, <0.01% as Half-life: - 3-12 hours unchanged drug) Excretion: - Renal LogP: - 0.91. [11] log P: - 1.5. [23] pKa: - 6.1.[12] pKa: - 6.4. [24] Nature: - Hydrophobic. [13] Nature: - Hydrophillic. [25] Uses: - It has been derivatized into the estrogen Uses: - treat various types of cancer. It is a chemotherapy analogue estramustine, used to treat prostate drug that works by slowing or stopping cell cancer.It can also be used in chemical warfare growth.Cyclophosphamide also works by decreasing your where it has the code-name HN2. This chemical is a immune system's response to various diseases. It is used to form of nitrogen mustard gas and a powerful treat a certain type of kidney disease in children after other vesicant. [2] treatments have not worked. [26] Dissolution profile: - Not available. Dissolution profile: - Not available. Cyclophosphamide. [14] Ifosfamide. [27] Systematic (IUPAC) name: - N-3-bis(2-chloroethyl)-1,3,2- Systematic (IUPAC) name: - N,N-bis(2- oxazaphosphinan-2-amide-2-oxide. chloroethyl)-1,3,2-oxazaphosphinan-2-amine2-oxide Chemical data: - Chemical data: - Molecular weight: - 261.1. [28] Formula: - C7H15Cl2N2O2P. [15] Molecular formula: - C7H15Cl2N2O2P. [29] Molecular Weight: - 261.088 g/mol. [16] Boiling Point: - 336.1 °C at 760 mmHg ... [30] Boiling point: - 407.5°C at 760 mmHg. [17] Melting point: - 39 - 41 C. [31] Melting point: - (monohydrate) 41-45°C. [18] Description: - white crystalline powder. [32] Description: - white colored powder which makes Solubility profile: - Freely soluble in water, very soluble in a colorless solution when dissolved. [19] alcohol, in ethyl acetate, in isopropyl alcohol, in methanol,in 419 Volume 2, Issue4,October- 2011 ethylene chloride, very slightly soluble in hexane. Molecular formula: - C14H19Cl2NO2. [41] [33][USP] Boiling Point: - 460.1 °C at 760 mmHg. [42] Mechanism of action: - The exact mechanism of Melting point: - 64℃. [43] ifosfamide has not been determined, but appears to Description: - off-white, slightly granular powder. [44] be similar to other alkylating agents. Ifosfamide Solubility profile: - Very slightly soluble in water, freely requires biotransformation in the liver by mixed- soluble in acetone, soluble in dilute alkali. [45][USP] function oxidases (cytochrome P450 system) before Soubility profile: - Freely soluble in ethanol(95%), in it becomes active. After metabolic activation, active acetone and in chloroform. Practically insoluble in water. metabolites of ifosfamide alkylate or bind with [46][IP] many intracellular molecular structures, including Mechanism of action: - Alkylating agents work by three nucleic acids. The cytotoxic action is primarily different mechanisms: 1) attachment of alkyl groups to DNA through the alkylation of DNA, done by attaching bases, resulting in the DNA being fragmented by repair the N-7 position of guanine to its reactive enzymes in their attempts to replace the alkylated bases, electrophilic groups. The formation of inter and preventing DNA synthesis and RNA transcription from the intra strand cross-links in the DNA results in cell affected DNA, 2) DNA damage via the formation of cross- death. [34] links (bonds between atoms in the DNA) which prevents Pharmacokinetic data DNA from being separated for synthesis or transcription, and Bioavailability: - 100%. [27] 3) the induction of mispairing of the nucleotides leading to Metabolism: - Hepatic. [27] mutations. [47] Half-life: - 60-80% in 72 hours. [27] Pharmacokinetic data Excretion: - Renal. [27] Bioavailability: - ? Log p: - 0.28. [35] Metabolism: - Hepatic Pka: - 4.75. [36] Half-life: - 1.5 hours Nature: - Hydrophobic. [37] Excretion: - N/A Uses: - Ifosfamide is used to treat various cancers pKa: - 5.8. [48] (such as testicular cancer). It works by slowing or LogP: - 3.25. [49] stopping the growth of cancer cells. OTHER This Nature: - Hydrophillic. [50] section contains uses of this drug that are not listed Uses: - It is used to treat cancer of the blood and lymph in the approved professional labeling for the drug system. It may also be used to treat other kinds of cancer, as but that may be prescribed by your health care determined by your doctor. professional. Use this drug for a condition that is Chlorambucil interferes with the growth of cancer cells, listed in this section only if it has been so which are eventually destroyed. Since the growth of normal prescribed by your health care professional. This body cells may also be affected by chlorambucil, other drug may also be used to treat other types of cancer effects will also occur. Some of these may be serious and (such as sarcomas, lung cancer). [38] must be reported to your doctor. Other effects may not be Dissolution profile: - Not available. serious but may cause concern. Some effects may not occur for months or years after the medicine is used. [51] Chlorambucil. [39] Dissloution profile; - Not available. Melphalan. [52] Systematic (IUPAC) name: - 4-[bis(2- chlorethyl)amino]benzenebutanoic acid. Chemical
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