Inclusion Complex of Fexofenadine Hydrochloride with Cyclodextrins

<p>Fexofenadine hydrochloride (FFN), (±)-4-[1-hydroxy-4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl] α,α-dimethylbenzeneacetic acid hydrochloride, is a second-generation antihistamine that is used to treat allergies. The drug is highly hydrophobic and slightly soluble in water. Cyclodextrins are widely used to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of poorly soluble drug molecules.Cyclodextrins can molecularly encapsulate various drugs into their hydrophobic cavity without forming any covalent bonds. Cyclodextrin (CDs), especially ß-Cyclodextrin (ß-CD), are widely used in the pharmaceutical field due to its ability to stabilize drug molecules and taste masking purposes.<strong> </strong></p><p>The phase solubility study was performed according to the method of Higuchi and Connors by adding the fexofenadine hydrochloride in excess to different concentrations of cyclodextrin solutions. Phase solubility study records show that the stability constant and complex stoichiometry of FFN-CD complexes increases linearly with CD concentration. Also, an increase in the concentration of β-cyclodextrin leads to an increase in the aqueous solubility of FFN. Complexes were analyzed by UV-VIS spectroscopy using the calibration curve of FFN. Also, UV-VIS spectra indicate a bathochromic shift which proves that complex formation has occurred.</p><p>Solid inclusion complexes of fexofenadine/β-cyclodextrin and its derivatives were prepared at the molar ratios of 1:1 by the physical mixing method. Characterization of the complexes was performed by using infrared spectroscopy. </p>

Study on the Complexation and Release Mechanism of Methylphenidate Hydrochloride Ion Exchange Resin Complex

Since the advent of ion exchange resin, it has been widely used in many fields, including drug delivery systems. The drug binds to the resin through an exchange reaction to form a drug–resin complex, which can gradually release drugs through the exchange of physiological ions in the gastrointestinal tract, to realize functions such as taste masking and regulating release. In this study, the complexes of methylphenidate hydrochloride and Amberlite IRP69 were prepared and evaluated to explore the mechanism of complexation, influencing factors and release mechanism at a molecular level. Firstly, with the properties of the selected complexes, molecular dynamics simulation was innovatively used to find that the intermolecular interaction between drug molecules and ion exchange resin molecules is mainly caused by the stacking effect of π and salt bridges. Secondly, with the drug loading status as an indicator, the factors affecting the compounding process of the drug and resin were explored. Finally, the release mechanism of the drug–resin complex was studied by mathematical model fitting. In summary, a variety of methods were used to study the mechanism of complexation and release between drug and resin, providing a theoretical basis for promoting the marketing of ion−exchange resin−mediated oral preparations.

Formulation and evaluation of taste masked oral disintegrating tablets of lornoxicam

Orally disintegrating tablets (ODT) disintegrate quickly with saliva when administered into the oral cavity and taken without water or chewed. ODT are easy to take for children and the elderly, who may experience difficultly in taking ordinary oral preparations such as tablets, capsules, and powders. The ODT threes substantial benefits for the patient (or elder) who cannot swallow (Dysphagia), or who is not permitted water intake due to disease. The reason of the current research was to prepare taste masking oral disintegrating tablets of poorly soluble lornoxicam (LXM) by direct compression technique using Kyron T-114 (cation exchange resin) as a taste masking agent. With in various ratios the Drug-resin of 1:4 was established to present best taste masking. The superdisintegrants used in formulation are croscarmellose sodium and cross povidone. Among these croscarmellose sodium demonstrated superior drug release. The tablets were evaluated for friability, weight variation, wetting time, hardness, disintegration time and uniformity of content. Optimized formulations were evaluated for in vitro dissolution test. Amongst all the formulations F-6 was found to be most successful tablets prepared by this technique had disintegration time of 30sec and % CDR 94.78 within 30min. Hence, this advance can be utilized for taste masking of bitter pharmaceutical ingredients leading to superior patient compliance. Keywords: Oral disintegration tablets, Lornoxicam, Kyron T-114, Superdisintegrants, Direct Compression.

Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use

Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and 1H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test.

Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery

The present study describes the use of two taste-masking polymers to fabricate a formulation of chlorpheniramine maleate for paediatric administration. Co-axial electrospinning was utilized to create layered nanofibres; the two polymers, Eudragit® E PO and Kollicoat® Smartseal, were alternated between the core and the shell of the system in order to identify the optimum taste-masked formulation. The drug was loaded in the core on all occasions. It was found that the formulation with Kollicoat® Smartseal in the core with the drug, and Eudragit® E PO in the shell showed the most effective taste-masking compared to the other formulations. These fibres were in the nano-range and had smooth morphology as verified by scanning electron microscopy. Solid-state characterization and thermal analysis confirmed that amorphous solid dispersions were formed upon electrospinning. The Insent E-tongue was used to assess the taste-masking efficiency of the samples, and it was found that this formulation was undetectable by the bitter sensor, indicating successful taste-masking compared to the raw version of the drug. The E-tongue also confirmed the drug’s bitterness threshold as compared to quinine HCl dihydrate, a parameter that is useful for formulation design and taste-masking planning.

Formulation and Evaluation of Mouth Dissolving Tablet of Almotriptan Malate

Mouth dissolving tablet disintegrates and dissolves rapidly in the saliva, within a few seconds without the need of drinking water or chewing. A mouth dissolving tablet usually dissolves in the oral cavity within 15 seconds to 3 minutes. Almotriptan malate is an anti migraine drug with bitter taste and shows hepatic metabolism. In the present work, Mouth dissolving tablets of almotriptan malate were prepared by direct compression method using sodium starch glycolate and croscarmellose sodium as superdisintegrant with a view to enhance patient compliance and to avoid gastric dysmotility which is common with migraine drugs and for fast action of drug. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water-absorption ratio and in-vitro dispersion time. Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and disintegration time. Keywords: Almotriptan malate, Superdisintegrant, Sodium starch glycolate, Crosscarmellose sodium, Taste masking.

FORMULATION, IN VITRO, AND IN VIVO EVALUATION OF TASTE-MASKED ORAL DISINTEGRATING TABLETS OF FEXOFENADINE HYDROCHLORIDE USING SEMISYNTHETIC AND NATURAL SUPERDISINTEGRANTS

Objective: The aim of the present research work was to prepare and evaluate taste-masked oral disintegrating tablets (ODT) of Fexofenadine hydrochloride. Methods: In the present work, Eudragit EPO, a taste masking agent and Karaya gum (GK) (natural), Sodium starch glycolate, and Croscarmellose sodium (CCS) (semi-synthetic) super disintegrants in three ratios (3, 6,9%) were used. Taste masked granules were prepared by different ratios of the drug: Eudragit EPO (1:1, 1:1.5, 1:2) by wet granulation method. The optimized taste-masked granules (1:2) were selected by sensory evaluation test to prepare 9 Fexofenadine ODT (FH1-FH9) formulations. These were evaluated for different parameters. Then desirability function (DF) was calculated for all formulations using disintegration time (DT), time taken for the tablet to release 90% of the drug (t 90%), and % drug dissolved in 10 min (Q10) as significant parameters. Results: The best formulation (FH6) showed the highest DF value due to less DT and 100% in vitro drug release within 15 min. Thus, FH6 formulation containing 9% CCS was selected as the best among the prepared formulations to which in vivo studies were performed on rabbits to find maximum plasma concentration (Cmax), time taken to reach maximum concentration (tmax), area under the curve (AUC), rate of elimination (Kel), absorption rate (Ka) and half-life(t1/2) and compared with Fexofenadine (Allegra) marketed tablets. Total bioavailability was increased for the test formulation compared to the reference formulation. Conclusion: Fexofenadine was successfully prepared as ODT with increased AUC and decreased tmax to which stability studies were conducted which were found to be stable.