Formulation and in vitro evaluation of taste-masked oro-dispersible dosage form of diltiazem hydrochloride

Abstract

Diltiazem hydrochloride is a calcium channel blocker generally indicated for the treatment of angina and hypertension, and it is extensively metabolized due to the hepatic metabolism. Formulation of diltiazem hydrochloride into an oro-dispersible dosage form can provide fast relief with higher bioavailability. The bitter taste of the drug should be masked to formulate it in a palatable form. In the present work, an attempt was made to mask the taste by complexation technique, with a formulation into an oro-dispersible dosage form, using superdisintegrants Doshion P544, crospovidone (CP) and sodium starch glycolate (SSG). The complexes of diltiazem hydrochloride with β-CD (1:1 molar ratio) were prepared by kneading, co-evaporation, co-grounding, freeze-drying and melting methods. Phase solubility showed stability constant 819.13M-1. Prepared inclusion complexes were evaluated for taste masking and characterized by I.R, XRD, DSC. Using the drug β-CD complex, oro-dispersible tablets were prepared and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), dissolution rate and taste. Formulations with 4 % Doshion, 8 % CP and 4 % SSG showed DT of 0.54, 0.35 and 1.23 minutes, respectively.Uniterms: Diltiazem hydrochloride. Cyclodextrin. Drugs/taste-masking. Freeze-drying.O cloridrato de diltiazem é bloqueador do canal de cálcio geralmente indicado para o tratamento de angina e de hipertensão e é extensamente biotransformado devido ao metabolismo hepático. A formulação do cloridrato de diltiazem em orodispersão pode prover rápida liberação com maior biodisponibilidade. O sabor amargo do fármaco deve ser mascarado para ser formulado em forma palatável. No presente trabalho tentou-se mascarar o sabor pela técnica de complexação, com uma orodispersão, usando superdesintegrantes, como Doshio P544, crospivodina (CP) e glicolato de amido sódico (SSG). Os complexos de cloridrato de diltiazem com β-CD (razão molar 1:1) foram preparados por mistura, coevaporação, comoagem, liofilização e métodos de fusão. A solubilidade de fase mostrou estabilidade constante de 819,13 M -1 . Os complexos de inclusão preparados foram avaliados com relação ao mascaramento do sabor e caracterizados por IV, Difração de Raios X e DSC. Empregando-se o fármaco complexado com β-CD, prepararam-se comprimidos dispersíveis e avaliaram-se os mesmos quanto à dureza, friabilidade, variação de peso, espessura, tempo de desintegração (DT), taxa de dissolução e sabor. Formulações com 4% de Doshion, 8% de CP e 4% de SSG mostraram DT de 0,54, 0,35 e 1,23 minutos, respectivamente. Unitermos: Cloridrato de diltiazem. Ciclodextrina. Fármacos/mascaramento de sabor. Liofilização.

Physical Approaches to Masking Bitter Taste: Lessons from Food and Pharmaceuticals

“…However, because of the speed of interaction, merely having the cyclodextrin in the formulation had the same effects as pre-forming the complex. In a similar approach, cyclodextrins were used to reduce the bitterness of diltiazem hydrochloride (58) and cetirizine (59) in orodispersible tablets.…”

Formulation, Preparation, and Evaluation of Novel Orally Disintegrating Tablets Containing Taste-Masked Naproxen Sodium Granules and Naratriptan Hydrochloride

“…The most effective approach is the addition of sweeteners and flavors combined with physical taste masking that prevents the interaction of the drug substance with taste buds . However, only incorporation of taste‐masked APIs into ODTs prepared by direct compression has been reported up to now . Different methodologies have been used to achieve proper taste masking of APIs, including spray drying with Eudragit® E, coating with hydroxypropylcellulose or Eudragit® RL30‐D, and granulation or extrusion with different excipients and polymers .…”

“…22,23 However, only incorporation of taste-masked APIs into ODTs prepared by direct compression has been reported up to now. [23][24][25][26][27][28][29][30] Different methodologies have been used to achieve proper taste masking of APIs, including spray drying with Eudragit R E, 29,30 coating with hydroxypropylcellulose 28 or Eudragit R RL30-D, 24 and granulation or extrusion with different excipients and polymers. 23,26,27 However, these taste masking methods result in particles or granules that have to be incorporated into the tablet matrix.…”

Preparation and in Vitro Evaluation of Cyclodextrin Based Effervescent and Dispersible Granules of Carbamazepine

“…The resulting mixture was stirred for 1 hour and evaporated at a temperature of 45 °C until dried. The dried mass was pulverized and sieved through sieve no.20 [10] The ternary complex comprising of 0.25% w/v (HPMC E5) was prepared by first dissolving required amounts of β-cyclodextrin and polymer in distilled water which was then added to the methanolic solution of carbamazepine [9]and then the same procedure was done like that for the binary system.…”

“…Experiment for the ternary system was performed analogously to those for the binary systems, but in the presence of 0.25% w/v HPMC E5 [9] After 48 h mixing, the samples were filtered through a millipore filter paper 0.45 μm., the concentration of the dissolved carbamazepine was determined spectrophotometrically at 284 nm.…”