Enhancing Dissolution and Bioavaibility of Purely Water Insoluble Natural Compounds by Solid Dispersion with Hot Melt Extrusion Technique

Sofi Nurmay Stiani, Taofik Rusdiana, Anas Subarnas

Abstract

The use of herbal remedies is still a trend in the world, especially Indonesia as the second largest country after Brazil is rich in medicinal plants, in addition to having many pharmacological properties also have low side effects. The most common problems with biopharmaceutically related natural substances are low drug solubility, low biopharmaceutics, stability problems and active substance absorption. Bioavailability is an important factor in achieving the effects of drug therapy. Low bioavailability may occur due to low water solubility, instability in the digestion, and difficulty passing through the membrane. To overcome the problem of bioavaibility of natural material compounds should be made efforts to improve it, one of them with solid dispersion method. The solid dispersion is the dispersion of one or more active ingredients in an inert solid carrier. Technique of Dispersion in the carrier can be by way of hot spin mixing, co-evaporation, co-precipttion, freeze-drying, spray drying and HME. Techniques that are still rarely used in Indonesia is hot melt extrusion (HME). This study aims to explore characteristics of the chemical properties of natural materials, efforts to increase the bioavailability of natural compounds, and solid dispersion techniques.

Keywords: Bioavailability, Natural compounds, solid dispersion, hot melt extrusion

Full Text:

PDF

References

Garima Jain and Umesh K.Patil, “Strategies For Enhancement Of Bioavaibility Of Medicinal Agents With Natural Products,” Indones. J. Pharm. Sci. Res., vol. 6, no. 12, pp. 5315–24, 2015.

C. A. Lipinski, “Drug-like properties and the causes of poor solubility and poor permeability,” J. Pharmacol. Toxicol. Methods, vol. 44, no. 1, pp. 235–249, 2000.

I. S. O. Dosage, “Guidance for Industry Guidance for Industry Waiver of In Vivo Bioavailability and,” Drugs, vol. FDA Guidan, no. August, p. 16, 2000.

J. Zhang, D. Liu, Y. Huang, Y. Gao, and S. Qian, “Biopharmaceutics classification and intestinal absorption study of apigenin,” Int. J. Pharm., vol. 436, no. 1–2, pp. 311–317, 2012.

N. El Husna, M. Novita, and S. Rohaya, “Anthocyanins Content and Antioxidant Activity of Fresh Purple Fleshed Sweet Potato and Selected Products,” Agritech, vol. 33, no. 3, pp. 296–302, 2013.

E. Abourashed, “Bioavailability of Plant-Derived Antioxidants,” Antioxidants, vol. 2, no. 4, pp. 309–325, 2013.

I. K. Alisha Amanda, “PENGARUH WAKTU MASERASI TERHADAP RENDEMEN ZAT ANTOSIANIN PEWARNA ALAMI MINUMAN JELLY DARI TERONG UNGU,” UMJ, 2017.

K. Yudiono, “Ekstraksi antosianin dari ubijalar ungu (Ipomoea batatas cv. ayamurasaki) dengan teknik ekstraksi subcritical water,” Teknol. pangan, vol. 2, no. 1, pp. 1–30, 2011.

M. A. S. Waldmann1 et al., “Provisional Biopharmaceutical Classification of Some Common Herbs Used in Western Medicine,” Mol. Pharm., vol. 9, no. 4, pp. 815–822, 2012.

M. P. (Translator) Brinckmannand, Josef A. & Lindenmaaier, Herbal Drugs and Phytopharmaceuticals (A Handbook for Practice on a Scientific Basis. Germany: medpharm Scientific Publishers, 2004.

L. Gallo, J. M. Llabot, D. Allemandi, V. Bucalá, and J. Piña, “Influence of spray-drying operating conditions on Rhamnus purshiana (Cáscara sagrada) extract powder physical properties,” Powder Technol., vol. 208, no. 1, pp. 205–214, 2011.

L. Y. Chung, “The Antioxidant Properties of Garlic Compounds: Allyl Cysteine, Alliin, Allicin, and Allyl Disulfide,” J. Med. Food, vol. 9, no. 2, pp. 205–213, 2006.

S. Quintero-Fabián, D. Ortuño-Sahagún, M. Vázquez-Carrera, and R. I. López-Roa, “Alliin, a garlic (Allium sativum) compound, prevents LPS-induced inflammation in 3T3-L1 adipocytes,” Mediators Inflamm., vol. 2013, 2013.

M. E. Rybak, E. M. Calvey, and J. M. Harnly, “Quantitative Determination of Allicin in Garlic: Supercritical Fluid Extraction and Standard Addition of Alliin,” J. Agric. Food Chem., vol. 52, no. 4, pp. 682–687, 2004.

S. Ankri and D. Mirelman, “Antimicrobial properties of allicin from garlic,” Microbes and Infection, vol. 1, no. 2. pp. 125–129, 1999.

Y. S. Kim, K. S. Kim, I. Han, M. H. Kim, M. H. Jung, and H. K. Park, “Quantitative and qualitative analysis of the antifungal activity of allicin alone and in combination with antifungal drugs,” PLoS One, vol. 7, no. 6, 2012.

H.-Y. Young, Y.-L. Luo, H.-Y. Cheng, W.-C. Hsieh, J.-C. Liao, and W.-H. Peng, “Analgesic and anti-inflammatory activities of [6]-gingerol,” J. Ethnopharmacol., vol. 96, no. 1–2, pp. 207–210, 2005.

H. S. Lee, E. Y. Seo, N. E. Kang, and W. K. Kim, “[6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells,” J. Nutr. Biochem., vol. 19, no. 5, pp. 313–319, 2008.

B. O. Ajayi, I. A. Adedara, and E. O. Farombi, “Pharmacological activity of 6-gingerol in dextran sulphate sodium-induced ulcerative colitis in BALB/c Mice,” Phyther. Res., vol. 29, no. 4, pp. 566–572, 2015.

Y. Xu et al., “Enhanced oral bioavailability of [6]-Gingerol-SMEDDS: Preparation, in vitro and in vivo evaluation,” J. Funct. Foods, vol. 27, pp. 703–710, 2016.

Q. Wang et al., “A novel formulation of [6]-gingerol: Proliposomes with enhanced oral bioavailability and antitumor effect,” Int. J. Pharm., vol. 535, no. 1–2, pp. 308–315, 2018.

R. Salea, B. Veriansyah, and R. R. Tjandrawinata, “Optimization and scale-up process for supercritical fluids extraction of ginger oil from Zingiber officinale var. Amarum,” J. Supercrit. Fluids, vol. 120, pp. 285–294, 2017.

J. Lu et al., “Immunosuppressive activity of 8-gingerol on immune responses in mice.,” Molecules, vol. 16, no. 3, pp. 2636–45, 2011.

J. Lu et al., “Immunosuppressive activity of 8-gingerol on immune responses in mice,” Molecules, vol. 16, no. 3, pp. 2636–2645, 2011.

H. Sato et al., “Ginger Extract-Loaded Solid Dispersion System with Enhanced Oral Absorption and Antihypothermic Action,” J. Agric. Food Chem., vol. 65, no. 7, pp. 1365–1370, 2017.

M. Park, J. Bae, and D. S. Lee, “Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria,” Phyther. Res., vol. 22, no. 11, pp. 1446–1449, 2008.

S. C. Ho, K. S. Chang, and C. C. Lin, “Anti-neuroinflammatory capacity of fresh ginger is attributed mainly to 10-gingerol,” Food Chem., vol. 141, no. 3, pp. 3183–3191, 2013.

E. Noor, L. Harmi, A. Maddu, and M. Yusron, “Fabrication of nanogingerol by combining phase inversion composition and temperature,” Res. J. Pharm. Biol. Chem. Sci., vol. 6, no. 1, pp. 38–47, 2015.

S. Shim, S. Kim, D. S. Choi, Y. B. Kwon, and J. Kwon, “Anti-inflammatory effects of [6]-shogaol: Potential roles of HDAC inhibition and HSP70 induction,” Food Chem. Toxicol., vol. 49, no. 11, pp. 2734–2740, 2011.

B. S. Tan et al., “6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ),” Cancer Lett., vol. 336, no. 1, pp. 127–139, 2013.

S. Ok and W. S. Jeong, “Optimization of extraction conditions for the 6-shogaol-rich extract from ginger (Zingiber officinale Roscoe),” Prev. Nutr. Food Sci., vol. 17, no. 2, pp. 166–171, 2012.

C. K. Wei et al., “6-paradol and 6-shogaol, the pungent compounds of ginger, promote glucose utilization in adipocytes and myotubes, and 6-paradol reduces blood glucose in high-fat diet-fed mice,” Int. J. Mol. Sci., vol. 18, no. 1, 2017.

C.-T. H. and M.-H. P. Po-Chuen Shieh, Yi-Own Chen, Daih-Huang Kuo, Fu-An Chen, Mei-Ling Tsai, Ing-Shing Chang, Hou Wu, Shengmin Sang, “Induction of Apoptosis by [8]-Shogaol via Reactive Oxygen Species Generation, Glutathione Depletion, and Caspase Activation in Human Leukemia Cells,” J. Agric. Food Chem, vol. 58, no. 6, pp. 3847–3854, 2010.

C. Y. Chen, K. C. Cheng, A. Y. Chang, Y. T. Lin, Y. C. Hseu, and H. M. Wang, “10-shogaol, an antioxidant from Zingiber officinale for skin cell proliferation and migration enhancer,” Int. J. Mol. Sci., vol. 13, no. 2, pp. 1762–1777, 2012.

F. Li et al., “In vitro antioxidant and anti-inflammatory activities of 1-dehydro-[6]-gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin,” Food Chem., vol. 135, no. 2, pp. 332–337, 2012.

S. R. Gundala et al., “Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract,” Carcinogenesis, vol. 35, no. 6, pp. 1320–1329, 2014.

A. S. Yalçin, A. M. Yılmaz, E. M. Altundağ, and S. Koçtürk, “Kurkumin, kuersetin ve çay kateşinlerinin anti-kanser etkileri,” Marmara Pharm. J., vol. 21, no. 1, pp. 19–29, 2017.

C. A. Edityaningrum and H. Rachmawati, “Peningkatan Stabilitas Kurkumin Melalui Pembentukan Kompleks Kurkumin-b-Siklodekstrin Nanopartikel Dalam Bentuk Gel,” Pharmaciana, vol. 5, no. 1, pp. 53–60, 2015.

J. Cui et al., “Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems,” Int. J. Pharm., vol. 371, no. 1–2, pp. 148–155, 2009.

L. Hu et al., “Enhancement of Oral Bioavailability of Curcumin by a Novel Solid Dispersion System,” AAPS PharmSciTech, vol. 16, no. 6, pp. 1327–1334, 2015.

A. Bakhtiar, S. R. Gaesari, and E. Zaini, “Pembentukan Kokristal Katekin dengan Nikotinamida,” J. Farm. Sains dan Terap., vol. 2, no. 2, pp. 28–32, 2015.

T. Anggraini, A. Tai, T. Yoshino, and T. Itani, “Antioxidative activity and catechin content of four kinds of Uncaria gambir extracts from West Sumatra , Indonesia,” African J. Biochem. Res., vol. 5, no. 1, pp. 33–38, 2011.

dan B. A. Syofyan, Lucida H, “Peningkatan Kelarutan Kuersetin Melalui Pembentukan Kompleks Inklusi dengan Siklodekstrin.,” J. Sains dan Teknol. Farm., vol. 13, no. 2, pp. 66–72, 2008.

A. Semalty, M. Semalty, D. Singh, and M. S. M. Rawat, “Phyto-phospholipid complex of catechin in value added herbal drug delivery,” J. Incl. Phenom. Macrocycl. Chem., vol. 73, no. 1–4, pp. 377–386, 2012.

F. Ali, Rahul, F. Naz, S. Jyoti, and Y. H. Siddique, “Health functionality of apigenin: A review,” Int. J. Food Prop., vol. 20, no. 6, pp. 1197–1238, 2017.

T. Rusdiana et al., “In Vitro Test of Anticalculi Effect from Celery herb (Apium graveolens L.),” Indones. J. Pharm. Sci. Technol., vol. 2, no. 2, pp. 63–67, 2015.

P. P. V. P. K-, “Uji sistem dispersi padat kofein dengan menggunakan polivinil pirolidon (pvp) k-30,” vol. 5, no. 2, pp. 166–177, 2013.

Y. Zhu et al., “Enhanced oral bioavailability of capsaicin in mixed polymeric micelles: Preparation, in vitro and in vivo evaluation,” J. Funct. Foods, vol. 8, no. 1, pp. 358–366, 2014.

S. K. Sharma, A. S. Vij, and M. Sharma, “Mechanisms and clinical uses of capsaicin,” European Journal of Pharmacology, vol. 720, no. 1–3. pp. 55–62, 2013.

Y. S. Chen, C. J. Liu, C. Y. Cheng, and C. H. Yao, “Effect of bilobalide on peripheral nerve regeneration,” Biomaterials, vol. 25, no. 3, pp. 509–514, 2004.

A. Mdzinarishvili, C. Kiewert, V. Kumar, M. Hillert, and J. Klein, “Bilobalide prevents ischemia-induced edema formation in vitro and in vivo,” Neuroscience, vol. 144, no. 1, pp. 217–222, 2007.

Y. H. Choi, J. Kim, and K. P. Yoo, “Supercritical-fluid extraction of bilobalide and ginkgolides from Ginkgo biloba leaves by use of a mixture of carbon dioxide, methanol, and water,” Chromatographia, vol. 56, no. 11–12, pp. 753–757, 2002.

K.-L. Wang et al., “Effects of ginkgolide A, B and K on platelet aggregation,” Zhongguo Zhongyao Zazhi, vol. 42, no. 24, 2017.

W. Wang et al., “Enhanced dissolution rate and oral bioavailability of Ginkgo biloba extract by preparing solid dispersion via hot-melt extrusion,” Fitoterapia, vol. 102, pp. 189–197, 2015.

L. Wang et al., “Enhanced dissolution rate and oral bioavailability of ginkgo biloba extract by preparing nanoparticles via emulsion solvent evaporation combined with freeze drying (ESE-FR),” RSC Adv., vol. 6, no. 81, pp. 77346–77357, 2016.

R. L. Ji, S. H. Xia, Y. Di, and W. Xu, “Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats,” World J. Gastroenterol., vol. 17, no. 17, pp. 2241–2247, 2011.

S. H. Xia and D. C. Fang, “Pharmacological action and mechanisms of ginkgolide B,” Chinese Medical Journal, vol. 120, no. 10. pp. 922–928, 2007.

P. Yang, X. Cai, K. Zhou, C. Lu, and W. Chen, “A novel oil-body nanoemulsion formulation of Ginkgolide B: Pharmacokinetics study and in vivo pharmacodynamics evaluations,” J. Pharm. Sci., vol. 103, no. 4, pp. 1075–1084, 2014.

C. J. Liou, X. Y. Lai, Y. L. Chen, C. L. Wang, C. H. Wei, and W. C. Huang, “Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signaling pathway,” Evidence-based Complement. Altern. Med., vol. 2015, 2015.

R. L. Edwards, T. Lyon, S. E. Litwin, A. Rabovsky, J. D. Symons, and T. Jalili, “Quercetin reduces blood pressure in hypertensive subjects.,” J. Nutr., vol. 137, no. 11, pp. 2405–11, 2007.

Y. Xiong et al., “Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats,” Diabetes, vol. 59, no. 10, pp. 2505–2512, 2010.

J. Xiong, J. Guo, L. Huang, B. Meng, and Q. Ping, “The use of lipid-based formulations to increase the oral bioavailability of panax notoginseng saponins following a single oral gavage to rats,” Drug Dev. Ind. Pharm., vol. 34, no. 1, pp. 65–72, 2008.

K. T. Lee, T. W. Jung, H. J. Lee, S. G. Kim, Y. S. Shin, and W. K. Whang, “The antidiabetic effect of ginsenoside Rb2 via activation of AMPK,” Arch. Pharm. Res., vol. 34, no. 7, pp. 1201–1208, 2011.

E. J. Kim, H. Il Lee, K. J. Chung, Y. H. Noh, Y. Ro, and J. H. Koo, “The Ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions,” BMB Rep., vol. 42, no. 4, pp. 194–199, 2009.

F. Yang et al., “Preparation and evaluation of self-microemulsions for improved bioavailability of ginsenoside-Rh1 and Rh2,” Drug Deliv. Transl. Res., vol. 7, no. 5, pp. 731–737, 2017.

D. H. Kim et al., “Ginsenoside Rc modulates Akt/FoxO1 pathways and suppresses oxidative stress,” Arch. Pharm. Res., vol. 37, no. 6, pp. 813–820, 2014.

T. Yu et al., “Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2,” J. Ginseng Res., vol. 41, no. 2, pp. 127–133, 2017.

L. Wang et al., “Immunosuppressive effects of ginsenoside-Rd on skin allograft rejection in rats,” J. Surg. Res., vol. 176, no. 1, pp. 267–274, 2012.

Y. Han and K. Y. Rhew, “Ginsenoside Rd induces protective anti-Candida albicans antibody through immunological adjuvant activity,” Int. Immunopharmacol., vol. 17, no. 3, pp. 651–657, 2013.

X.-D. Liu, B. Wang, W. Li, Y. Bai, S.-X. Hou, and G. Zhao, “Effect of ginsenoside-Rd on the prognosis of acute ischemic stroke,” J. Xi’an Jiaotong Univ. (Medical Sci., vol. 34, no. 1, 2013.

J. E. K. Hyeongmin Kim , q, Jong Hyuk Lee , q et al., “Micro-/nano-sized delivery systems of ginsenosides for improved systemic bioavailability,” J. Ginseng Res., pp. 1–9, 2018.

W. C. S. Cho, W. S. Chung, S. K. W. Lee, A. W. N. Leung, C. H. K. Cheng, and K. K. M. Yue, “Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats,” Eur. J. Pharmacol., vol. 550, no. 1–3, pp. 173–179, 2006.

M. K. Kim et al., “Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain,” J. Ginseng Res., vol. 42, no. 2, pp. 183–191, 2018.

D. H. Kim, G. R. Ryu, O. C. Lee, M. H. Yeom, and J. C. Cho, “Topical composition comprising ginsenoside Rf for improving anti-acne effect and promoting hair growth.,” 2014.

B. M. & Q. P. Jing Xiong, Jianxin Guo, Luosheng Huang, “The Use of Lipid-Based Formulations to Increase the Oral Bioavailability of Panax Notoginseng Saponins Following a Single Oral Gavage to Rats,” Drug Dev. Ind. Pharm., vol. 34, no. 1, pp. 65–72, 2008.

B. Kenarova, H. Neychev, C. Hadjiivanova, and V. D. Petkov, “Immunomodulating activity of ginsenoside Rg1 from Panax ginseng.,” Jpn. J. Pharmacol., vol. 54, no. 4, pp. 447–454, 1990.

Y. Cheng, L. H. Shen, and J. T. Zhang, “Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action,” Acta Pharmacologica Sinica, vol. 26, no. 2. pp. 143–149, 2005.

J.-M. Tian, J. Liu, H. Li, J.-M. Ye, and L.-Y. Li, “Effects of ginsenoside Rg2 on cerebral circulation and brain edema,” Chinese J. New Drugs, vol. 18, no. 17, 2009.

M. Tian, W. Bi, and K. H. Row, “Solid-phase extraction of liquiritin and glycyrrhizic acid from licorice using ionic liquid-based silica sorbent,” J. Sep. Sci., vol. 32, no. 23–24, pp. 4033–4039, 2009.

J. Y. Yu, J. Y. Ha, K. M. Kim, Y. S. Jung, J. C. Jung, and S. Oh, “Anti-inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver,” Molecules, vol. 20, no. 7, pp. 13041–13054, 2015.

P. Kidd and K. Head, “A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos??),” Alternative Medicine Review, vol. 10, no. 3. pp. 193–203, 2005.

K. Flora, M. Hahn, H. Rosen, and K. Benner, “Clinical review: Milk thistle (Silybum marianum) for the therapy of liver disease,” Am. J. Gastroenterol., vol. 93, pp. 139–143, 1998.

L. Kole, B. Giri, S. K. Manna, B. Pal, and S. Ghosh, “Biochanin-A, an isoflavon, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFκB nuclear translocation,” Eur. J. Pharmacol., vol. 653, no. 1–3, pp. 8–15, 2011.

X. Wu et al., “Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing pluronic F127 and plasdone S630,” Int. J. Nanomedicine, vol. 12, pp. 1475–1483, 2017.

G. P. Ramos et al., “In vivo and in vitro anti-inflammatory activity of red clover Trifolium pratense dry extract,” Rev. Bras. Farmacogn., vol. 22, no. 1, pp. 176–180, 2012.

Y. Ge, X. Wang, W. Guo, and X. Xie, “Preparation of water-soluble chitosan solid dispersion of daidzein,” Zhongguo Zhong Yao Za Zhi, vol. 35, no. 3, pp. 293–296, 2010.

P. B. Clifton-Bligh et al., “Red clover isoflavones enriched with formononetin lower serum LDL cholesterol—a randomized, double-blind, placebo-controlled study,” Eur. J. Clin. Nutr., vol. 69, no. 1, pp. 134–142, 2014.

J. Xu and K. Q. Luo, “Enhancing the solubility and bioavailability of isoflavone by particle size reduction using a supercritical carbon dioxide-based precipitation process,” Chem. Eng. Res. Des., vol. 92, no. 11, pp. 2542–2549, 2014.

L. Omur Demirezer, N. Karahan, E. Ucakturk, A. Kuruuzum-Uz, Z. Guvenalp, and C. Kazaz, “HPLC fingerprinting of sennosides in laxative drugs with isolation of standard substances from some senna leaves,” Rec. Nat. Prod., vol. 5, no. 4, pp. 261–270, 2011.

L. R. Jat, “Hyperforin: A potent anti-depressant natural drug,” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 5, no. SUPPL 3. pp. 9–13, 2013.

R. Nosratabadi, M. Rastin, M. Sankian, D. Haghmorad, and M. Mahmoudi, “Hyperforin-loaded gold nanoparticle alleviates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating regulatory T cells,” Nanomedicine Nanotechnology, Biol. Med., vol. 12, no. 7, pp. 1961–1971, 2016.

J. B. Hudson, I. Lopez-Bazzocchi, and G. H. N. Towers, “Antiviral activities of hypericin,” Antiviral Res., vol. 15, no. 2, pp. 101–112, 1991.

M. Zeisser-Labouèbe, N. Lange, R. Gurny, and F. Delie, “Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer,” Int. J. Pharm., vol. 326, no. 1–2, pp. 174–181, 2006.

Z.-J. Wang, S.-M. Lin, and M.-L. Hu, “Contents of hypericin and pseudohypericin in five commercial products of St John’s wort (Hypericum perforatum).,” J. Sci. Food Agric., vol. 84, no. 5, pp. 395–397, 2004.

K. T. Savjani, A. K. Gajjar, and J. K. Savjani, “Drug Solubility: Importance and Enhancement Techniques,” ISRN Pharm., vol. 2012, pp. 1–10, 2012.

C. B. R. Kommu Arun, Chebrolu Jayakishore Babu, P Laksmaiah and B. R. and P. Harshavardhan, “TECHNIQUES TO IMPROVE THE ABSORPTION OF POORLY SOLUBLE DRUGS,” Int. J. Res. Pharm. Chem., vol. 2, no. 2, pp. 533–540, 2012.

N. Arunkumar, M. Deecaraman, and C. Rani, “Nanosuspension technology and its applications in drug delivery,” Asian J. Pharm., vol. 3, no. 3, p. 168, 2009.

J. Pardeike, A. Hommoss, and R. H. Müller, “Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products,” International Journal of Pharmaceutics, vol. 366, no. 1–2. pp. 170–184, 2009.

M. Dittgen, S. Fricke, H. Gerecke, and H. Osterwald, “Hot spin mixing - A new technology to manufacture solid dispersions. Part 3: Progesterone,” Pharmazie, vol. 50, no. 7, pp. 507–508, 1995.

M. Dittgen, S. Fricke, H. Gerecke, and H. Osterwald, “Hot spin mixing--new technology to manufacture solid dispersions. Part 1. Testosterone,” Pharmazie, vol. 50, no. Mar, pp. 225–226, 1995.

R. P. Patel, M. P. Patel, and A. M. Suthar, “Spray drying technology: An overview,” Indian J. Sci. Technol., vol. 2, no. 10, pp. 44–47, 2009.

R. Chokshi and H. Zia, “Hot-Melt Extrusion technique: A Review,” Iran. J. Pharm. Res., vol. 3, no. December 2003, pp. 3–16, 2004.

H. Patil, R. V. Tiwari, and M. A. Repka, “Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation,” AAPS PharmSciTech, vol. 17, no. 1, pp. 20–42, 2016.

R. Bottom, “HME_ThermoFisher,” pp. 1–39, 2011.

M. Kolter, Karl and Karl, “Suitability of Plasticized Polymers for Hot Melt Extrusion,” Exipients&Actives For Pharma, vol. No.24, BASF SE Pharma Ingredients & Services, pp. 2–6, 2010.

I. Sridhar, A. Doshi, B. Joshi, V. Wankhede, and J. Doshi, “Solid Dispersions: an Approach to Enhance Solubility of poorly Water Soluble Drug,” J. Sci. Innov. Res. JSIR, vol. 2, no. 23, pp. 685–694, 2013.

S. A. Mogal, P. N. Gurjar, D. S. Yamgar, and A. C. Kamod, “Solid dispersion technique for improving solubility of some poorly soluble drugs,” Der Pharm. Lett., vol. 4, no. 5, pp. 1574–1586, 2012.

S. Sareen, L. Joseph, and G. Mathew, “Improvement in solubility of poor water-soluble drugs by solid dispersion,” Int. J. Pharm. Investig., vol. 2, no. 1, p. 12, 2012.

N. Saffoon, R. Uddin, N. H. Huda, and K. B. Sutradhar, “Enhancement of oral bioavailability and solid dispersion: A review,” J. Appl. Pharm. Sci., vol. 1, no. 7, pp. 13–20, 2011.

A. F. dan M. M. Lannie Hadisoewignyo, “Pembuatan garam ibuprofen dan aplikasinya dalam sediaan tablet,” Majalah Farmasi Indonesia, pp. 141–150, 2009.

S. BUDIPRATIWI WISUDYANINGSIH and A. K. NUGROHO, “Pengaruh pH dan Kekuatan Ionik terhadap Profil Kelarutan Ofloksasin,” ilmu kefarmasian Indones., vol. 12, no. 1, pp. 25–31, 2014.

N. Qiao, M. Li, W. Schlindwein, N. Malek, A. Davies, and G. Trappitt, “Pharmaceutical cocrystals: An overview,” International Journal of Pharmaceutics, vol. 419, no. 1–2. pp. 1–11, 2011.

P. Renkoğlu et al., “Indomethacin-saccharin cocrystal: Design, synthesis and preliminary pharmaceutical characterization,” Int. J. Pharm., vol. 104, no. 3, pp. 1560–1568, 2013.

Refbacks

  • There are currently no refbacks.