Modified release bi-layered tablet of melatonin using β-cyclodextrin

Department of Pharmaceutics, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Pharmazie (Impact Factor: 1.05). 10/2003; 58(9):642-4.
Source: PubMed


A modified release bi-layered tablet of melatonin incorporating a fast release fraction consisting of melatonin-beta-cyclodextrin inclusion complex and a slow release fraction containing melatonin in HPMC K15M and Carbopol 971 P matrices was prepared. The formulation developed showed an initial burst followed by a near zero order release pattern for a period of 8 h. The drug content, physical characteristics and the release profile were unaffected after 3 months of an accelerated stability study at 40 degrees C and 75% relative humidity.

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    • "CDs enhance the solubility of the drugs by the hollow truncated, cone like structure which encapsulates the hydrophobic drug molecules in the apolar interior. In contrast, the outer hydrophilic region enables solubilization through interaction with water (Kumar et al., 2003). 2-Hydroxypropyl-b-cyclodextrin (HPbCD) is a hydroxyalkyl-b-cyclodextrin derivative which is widely studied in drug encapsulation applications due to its high water solubility (Gould and Scott, 2005; Araujo et al., 2007; Başba g et al., 2014). "
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    ABSTRACT: In this study, melatonin/2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex was prepared by using microwave irradiation in a very short time. Phase-solubility studies indicated a linear increase in the solubility of melatonin with HPβCD demonstrating Higuchi's AL-type phase solubility profiles and the formation of 1:1 stoichiometric inclusion complexes. Also, the ability of inclusion complex formation was promoted at microwave conditions compared to room conditions. The structure of inclusion complex was determined by FTIR, DSC, XRD, (1)H NMR and (13)C NMR studies. Both of pure melatonin and melatonin/HPβCD inclusion complex were loaded into the chitosan scaffolds that were prepared by freeze-drying method and the effect of released melatonin on human osteosarcoma cells (MG-63) was investigated in vitro. Approximately 9mM melatonin concentration caused time dependent cell death by reducing the proportion of the cells in the G2/M phase rather than S phase. In conclusion, melatonin/HPβCD inclusion complex loaded chitosan scaffolds could be considered as an alternative system for the human osteosarcoma therapy.
    Full-text · Article · Nov 2015 · International Journal of Pharmaceutics
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    • "Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which have been investigated to improve the solubility and dissolution rate of various poorly soluble drugs [18–20]. Moreover, CDs have been successfully employed to modify the release pattern of drugs in several modified-release formulations [21–23]. In addition, it has been reported that the β-cyclodextrin (β-CD) has been most widely used to improve the oral bioavailability of poorly water-soluble drugs [24–29]. "
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    ABSTRACT: The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β -cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet.
    Full-text · Article · Jan 2014
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    • "Melatonin has a very short half-life and low and variable oral bioavailability presumably due to variable degrees of absorption and/or an extensive metabolism by the liver [7,8]. Furthermore, melatonin is a poorly water-soluble substance and has slow dissolution characteristics [9]. Hence, melatonin is not a good candidate for conventional oral immediate-release dosage forms [8]. "
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    ABSTRACT: The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% (w/v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.
    Full-text · Article · May 2012 · Nanoscale Research Letters
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