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12 protocols using maisine 35 1

1

Solid Solution Composition of Pentoxifylline

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Example 12

This example illustrates how to make a solid solution pharmaceutical composition disclosed herein comprising Pentoxifylline.

To prepare a solid solution pharmaceutical composition disclosed herein using Pentoxifylline, the following method was performed. About 208 mg Pentoxifylline, about 1.0 mL MAISINE® 35-1 (Gattefosse), a glyceryl monolinoleate (as room temperature liquid lipid), and about 0.2 mL isosorbide dimethyl ester (as stabilizing agent) were added to a vessel and heated to about 50° C. to about 60° C. with stirring until all components of the mixture were dissolved. About 1.0 g GELUCIRE®43/01 (Gattefosse), a waxy solid (as room temperature solid lipid) having a melting point of between 41° C. to 45° C. and comprising a mixture of saturated C10-C18 triglycerides, was added to this solution and stirred until incorporated. The heated mixture was then cooled to about 37° C. to about 40° C., and aliquoted by pouring into molds and cooled to room temperature. Alternatively, the mixture can be cooled to room temperature and then subsequently reheated to about 40° C. to about 45° C. for aliquoting into molds. The formulation solidified with a clear appearance and remelted without forming a precipitate. These results indicate that a solid solution formulation as disclosed herein comprising Pentoxifylline was formed.

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2

Tobramycin Nanoemulsion Formulation

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Tobramycin (TOB) was a gift sample from Welmark Pharmaceuticals (Hattar, Pakistan). Docusate sodium (DOC), sodium dodecanoate (DOD), Propylene glycol and acetonitril were obtained from Sigma-Aldrich (Darmstadt, Germany). Peceol (glycerol monooleate, HLB = 3), Cremophor RH (castor oil, hydrogenated, ethoxylated) and Maisine 35–1 (glycerol monolinoleate, HLB = 1) were a gift from Gattefossé (Lyon France).
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3

Formulation and Characterization of Gefitinib-Loaded Lipid-Based Nanocarriers

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Gefitinib (GEF) was purchased from Beijing Mesochem Technology Co., Ltd., (Beijing, China). Pluronic-F68 was purchased from Sigma Aldrich, (St. Louis, MO, USA). Stearic acid (SA) was purchased from BDH, (Poole, UK). Oleic acid (LCFA) was obtained from Avonchem, (Cheshire, UK). Maisine 35-1 (LCM) was purchased from Gattefossé, Saint Priest, France. Soybean (LCT) was generously provided by John L. Seaton & Co., Ltd., Croda International Plc., (East Yorkshire, UK).
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4

Optimization of Terconazole Topical Formulations

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Terconazole was supplied as a gift from Marcyrl Pharmaceutical Industries (Cairo, Egypt). Labrafil®M2125 CS, Capryol90, Labrasol®, Transcutol® HP, Lauroglycol90 and Maisine35-1 were kindly donated by Gattefosse (Lyon, France). Miglyol®812 was donated from Cremer Oleo division (Hamburg, Germany). Cremophor®RH40 was donated by BASF (Ludwigshafen, Germany). Captex®8000 was a gift from Abitec Corporation, Janesville. Tween®80, methanol, ethanol, sodium hydroxide, sodium dihydrogen phosphate, sodium lauryl sulphate, glycerin and propylene glycol were obtained from Adwic, El-Nasr pharmaceutical chemicals Co. (Cairo, Egypt). All reagents and solvents used in this study were of analytical grade.
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5

In Vitro Permeability Assessment of Pharmaceutical Formulations

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The CA was gifted by Ranbaxy (Mohali, India). Tween 20®, ethyl oleate, eucalyptus oil, propylene glycol, polyethylene 400 (PEG 400), castor oil, dimethyl sulfoxide ≥99.5% (DMSO), thiazolyl blue tetrazolium bromide 98% (MTT) and methylcellulose were purchased from Sigma-Aldrich (St. Louis, MO, USA). Tween 80®, soybean oil and olive oil were purchased from R&M Chemicals Ltd. (Essex, UK). Capmul MCM EP was obtained from the Abitec Corporation (Janesville, WI, USA). Peceol and Maisine 35-1 were obtained from Gattefosse (Saint-Priest, France). Cremophor EL® was obtained from BASF (Ludwigshafen, Germany). The dialysis membrane (MWCO 12,000 g/mole) was obtained from Sigma-Aldrich Sdn Bhd, Petaling Jaya, Malaysia. The Caco-2 cell line was bought from the American Type Culture Collection (ATCC) (Manassas, VA, USA). Dulbecco’s modified eagle’s medium (DMEM) was purchased from GE Healthcare Life Sciences (Logan, UT, USA). Trypsin 0.25% was purchased from GE Healthcare Life Sciences (Logan, UT, USA). The penicillin-streptomycin solution (100×) was obtained from Biowest (Nuaillé, France). Fetal bovine serum (FBS) and Dulbecco’s phosphate-buffered saline (DPBS) were purchased from Thermo Fisher Scientific (Waltham, MA, USA). The passive lysis buffer (5×) was purchased from Promega (Madison, WI, USA).
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6

Bioavailability Enhancement of Lipophilic Drugs

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The model drugs, SN (purity 99.9%) and DN, reference standard (purity >99.8%) were obtained as a gift from Renata (former Pfizer), and Concord Pharmaceuticals Ltd (Dhaka, Bangladesh), respectively. BSO was extracted directly by cold pressing method (mentioned in the method section) from naturally obtained Nigella sativa seeds. Capmul MCM (C10) mono-/di-glycerides of capric acid was purchased from Abitec Corp. (Janesville, USA). Soybean oil (SBO; long chain triglycerides) was obtained from John L. Seaton and Co. Ltd. (North Humberside, UK). Maisine 35-1 (long chain mono-glycerides) was donated by Gattefosse SAS, (Saint Priest, France). Cremophor EL was purchased from BASF, (Ludwigshafen, Germany). Porcine pancreatin (8XUSP specifications) was purchased from Sigma Chemical Co. (St Louis, MO, USA). HPLC grade methanol, acetonitrile, formic acid, and phosphoric acid were obtained from BDH Chemicals Ltd., (Poole, UK). High purity deionized water was obtained through a Milli-Q Integral Water Purification System (Millipore, Bedford, MA). All other reagents were used as of analytical grade without further purification.
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7

Formulation and Characterization of Propofol Nanoemulsions

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Propofol (purity 99.9%) was obtained from Incepta Pharmaceuticals Ltd. (Dhaka, Bangladesh). Zanthoxylum rhetsa seed oil (ZRO) was collected by a steam distillation process from naturally obtained seeds (no organic solvent was used). Medium-chain triglycerides (carbon chain length 8–12), Miglyol 810 (M810), and corn oil (CO) were purchased from Sasol Germany GmbH (Werk, Witten, Germany). Capmul MCM (C10) mono/diglycerides of capric acid were purchased from Abitec Corp. Janesville, USA. Maisine 35–1 (long-chain monoglycerides) was obtained from Gattefosse SAS, (Saint-Priest, France). Kolliphor ELP and Kolliphor HS15 were purchased from BASF, Ludwigshafen, Germany. Tween 80 (polyoxyethylene sorbitan monooleate) was obtained from Sigma Aldrich, USA. HPLC-grade acetonitrile, methanol, formic acid, and phosphoric acid were obtained from BDH Chemicals Ltd., Poole, UK. Milli-Q water was obtained through a Milli-Q Integral Water Purification System (Millipore, Bedford, MA). All other reagents were of analytical grade and used without further purification.
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8

Lipid-based Carrier Formulation Development

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KME (Fujian medical university, purity 99.2%). Capryol® 90, Labrasol, Maisine 35–1 and Transcutol® HP were purchased from Gattefossé (Shanghai) Co., LTD.; Cremophor® RH40 and Kolliphor EL were obtained from BASF (Germany). Medium chain triglyceride (MCT), Tween-80, Tween-20, propylene glycol, PEG 400, DIR dye and Coumarin-6 were all purchased from Sinopharm Chemical Reagents Co., LTD; Dulbecco’s Modified Eagle’s Medium (DMEM) and fetal bovine serum (FBS) were purchased from HyClone Inc.
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9

Nanoparticle-based Transdermal Drug Delivery

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Nimodipine and nifedipine were obtained as a gift sample from
Astron Research Ltd., Ahmedabad, India. Carbopol 934 P was obtained as a gift
sample from Lubrizol Advanced Materials India Pvt. Ltd., Mumbai, India. Capmul MCM
was purchased from Abitec Corporation, Janesville WI. Labrafil M 1944 CS, Peceol,
Maisine 35-1, Labrasol and Transcutol P were purchased from Gattefosse, France.
PEG 400, Pluronic F 68 and 127 were purchased from Sigma-Aldrich Co., MO, USA.
Tween 80 was obtained from S.D. Fine Chemicals, Mumbai, India. Sodium hydroxide
and potassium dihydrogen ortho-phosphate (analytical grade) were obtained from
Qualigen Fine Chemicals, Mumbai, India. All the solvents and chemicals used for
the study were of chromatographic grade and purchased from Qualigen Fine
Chemicals, Mumbai, India. Heparin was purchased from Biological E. Ltd.,
Hyderabad, India. Heparinised capillaries were purchased from Himedia, Mumbai,
India. Deionized water for HPLC was prepared in-house using a Milli-Q water
purifier system (Millipore Elix, Germany).
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10

Development and Evaluation of Solubility-Enhanced Hydrochlorothiazide Formulations

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Hydrochlorothiazide was received as a gift sample from Torrent Pharmaceuticals Ltd., Ahmedabad, India. Maisine 35-1, Transcutol P, and Lauroglycol 90 were generously provided by Gattefosse, France. Cremophor RH 40 and Cremophor EL were received as gift sample from BASF, USA. Captex 355 EP/NF, Captex 300 EP/NF, and Capmul MCM NF were a generous gift from Abitec Corporation, USA. Polyethylene glycol 400 (PEG 400) was purchased from Merck Limited, Mumbai, India. Oleic acid was purchased from S. D. Fine Chemicals Limited, Mumbai. Propylene glycol and Tween 80 were purchased from Thomas Baker Chemicals Limited, Mumbai. Castor oil USP was purchased from Arora Pharmaceuticals Private Limited, New Delhi. Empty hard gelatin capsules were obtained from Associated Capsules Pvt. Ltd, Mumbai. Dialysis Tubing (seamless cellulose tubing, MWCO 12000) was purchased from Sigma Chemical Co., USA. All other chemicals used were of analytical grade.
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