OPTIMIZATION OF DILTIAZEM HYDROCHLORIDE NANOPARTICLES FORMULA AND ITS RELEASE KINETICS EVALUATION

Objective: The purpose of this study was to determine the optimum formula of diltiazem HCl-loaded chitosan nanoparticles due to variations in the speed and duration of stirring and evaluating the release kinetics in vitro using DDSolver. Methods: The method used to prepare nanoparticles is ionic gelation. The ionic gelation method involves an ionic cross-linking between cations on the backbone of chitosan and anion, such as sodium tripolyphosphate (Na TPP). Results: Stirring speed of 1200 rpm and stirring time of 2 h produce an optimum response. The optimum formula has an entrapment efficiency of 71.10%, a particle size of 110.2 nm, and a polydispersity index of 0.268. The dry powder of diltiazem HCl nanoparticles produced a drug loading of 66.14±1.71% and a yield of 34.07±0.73%. The FT-IR showed ionic interaction (cross-linking) between ammonium ions from chitosan and phosphate ions from Na TPP. Scanning electron microscopy (SEM) analysis showed a particle size of 150 µm, a spherical shape, and rough surface morphology. In vitro release profiles indicated prolonged release, which follows the Korsmeyer Peppas model. Conclusion: It can be concluded that increasing the speed and duration of stirring will improve drug entrapment and reduce the particles size variation. The dry nanoparticles release mechanism is by diffusion and matrix erosion.

Optimization of Hydroxy Propyl Methyl Cellulose and Carbomer In Diltiazem Hydrochloride Mucoadhesive Buccal Film

Diltiazem hydrochloride (HCl) is a category of calcium channel blocker used as an antihypertensive agent. Diltiazem HCl is a low bioavailable drug due to high first-pass metabolism and a short half-life (3-5 hours); hence mucoadhesive buccal film was made to overcome this weakness. Bioavailability of Diltiazem HCl increase if the buccal preparations can contact the mucosa for a sufficient time. Therefore, in this study, two polymers are combined to obtain good film characteristics, especially residence time and mucoadhesive strength. This study was aimed to optimize Hydroxy Propyl Methyl Cellulose (HPMC) and Carbomer's amount in Diltiazem HCl mucoadhesive buccal film. The formulas were prepared by the solvent casting method and optimized with design expert software. The release kinetics and mechanism were evaluated using DDSolver program. The optimum amount of polymer obtained from optimization was 40 mg of HPMC and 10 mg of Carbomer. The optimum formula's swelling index was 4.18. The mucoadhesive strength was 53.07 gF, and the mucoadhesive residence time was 529.33 min. The FTIR spectra showed there was no interaction between Diltiazem HCl and other excipients. Thus it did not disturb the therapeutic effect. Based on the DDSolver statistical parameters and curve-fitting, the dissolution model of Diltiazem HCl from buccal mucoadhesive film follows Korsmeyer-Peppas. The release exponent (n) is 0.55, which shows a non-fickian/anomalous diffusion release mechanism. These mechanisms represent drug release controlled by a combination of diffusion and erosion.

Optimasi Hidroksipropil Metilselulosa dan Polivinil Pirolidon dalam Sediaan Mucoadhesive Buccal Film Diltiazem Hidroklorida

Diltiazem HCl is a class of benzodiazepine calcium channel blockers used to treat angina pectoris, arrhythmias, and hypertension. Diltiazem HCl improves first-pass metabolism, a short half time of 3-5 hours, and bioavailability of diltiazem for oral administration of about 40%. Mucoadhesive buccal film diltiazem HCl releases the drug to the buccal mucosa, so the first pass metabolism can be avoided because of its absorption through the venous system that flows from the cheek. This study aimed to study HPMC polymers and polyvinyl pyrrolidone (PVP) polymers on swelling index, residence time, mucoadhesive strength of mucoadhesive buccal film diltiazem HCl, FTIR, and drug release. The prepared film was evaluated for swelling index, mucoadhesive strength, and mucoadhesive residence time. The optimal amount for HPMC was 35 mg, and PVP was 15 mg. The combination of polymers with this amount can produce a swelling index was 3,00, mucoadhesive strength was 41,87 gF, and mucoadhesive residence time was 330,66. FTIR test indicated that there was no interaction between active function clusters of Diltiazem HCl and other excipients. The release of the optimum formula in the 360th minute was about 97.847%, following in the zero-order release model and Higuchi.

An Optimasi Polivinil Pirolidon dan Kitosan dalam Sediaan Mucoadhesive Buccal Film Diltiazem HCl

Diltiazem HCl adalah golongan benzoatiazepin penghambat kanal kalsium (calcium channel blocker) yang digunakan dalam pengobatan angina pektoris, aritmia, dan hipertensi. Diltiazem HCl mengalami first pass metabolism di hati, waktu paruh yang pendek yakni 3-5 jam dan bioavailabilitas diltiazem pada pemberian oral sekitar 40%. Sediaan mucoadhesive buccal film diltiazem HCl melepaskan obat ke mukosa buccal sehingga dapat menghindari first pass metabolism karena absorpsinya melalui sistem vena yang mengalir dari pipi. Tujuan penelitian ini adalah untuk mengetahui pengaruh polimer polivinil pirolidon (PVP) dan kitosan terhadap swelling index, waktu tinggal dan kekuatan mucoadhesive diltiazem HCl dalam sediaan mucoadhesive buccal film diltiazem HCl. Sediaan film dilakukan evaluasi swelling index, kekuatan mucoadhesive dan waktu tinggal mucoadhesive. Jumlah optimum untuk PVP adalah 1 mg dan kitosan sebesar 25 mg. Kombinasi polimer dengan jumlah tersebut dapat menghasilkan swelling index, kekuatan mucoadhesive, dan waktu tinggal mucoadhesive yaitu 3,641; 63,867 gF; dan 352,667 menit dan nilai desirability tertinggi yaitu 0,727. Kata kunci: mucoadhesive buccal film, diltiazem HCl, PVP, kitosan

Optimasi Hydroxypropyl Methylcellulose dan Chitosan pada Tablet Floating-Mucoadhesive Diltiazem Hidroklorida Menggunakan Desain Faktorial

Diltiazem HCl is one of the drugs used for hypertension treatment. It requires frequent dosing, which is why diltiazem HCl needs to be formulated into preparations using a controlled release drug delivery system. The combination of floating and the mucoadhesive system is expected to increase the stomach's retention of the dosage form. This study aimed to determine the optimum composition of hydroxypropyl methylcellulose (HPMC K100M) and chitosan for floating mucoadhesive diltiazem HCl tablet. Tablets that have been prepared were evaluated for the tablet's physical characterization, powder flowability test, dissolution test, floating ability, and mucoadhesive test. Tablets were optimized using a factorial design, and the data were analyzed using design expert 11.0.0. The results showed that the optimum formula for polymer combination in diltiazem HCl tablet was 175 mg for HPMC K100M and 50 mg for chitosan. The combination of polymers with this amount can produce a floating lag time of 45,333 seconds, floating duration time >12 hours, and the strength of mucoadhesive is 81,633 grams.

Optimization and Characterization of Fenugreek Seed Polymer Nanoparticles Loaded with Diltiazem HCl Nanoparticles by Desolvation Method

The main aim of the present investigation is to optimize and evaluate the fenugreek seed polymer nanoparticles using Diltiazem HCl as a model drug because Diltiazem HCl has short half-life. Nanoparticles were prepared by using desolvation method and evaluated to study the influence of polymer concentration and stirring speed on different characteristics of nanoparticles such as particle size, surface morphology, zeta potential, Encapsulation efficiency and In-vitro drug release. FTIR, DSC and XRD studies were also performed to determine the compatibility, degradation and crystalline nature of drug before and after formulation of nanoparticles. F7 (1:2 polymer concentration and 600 stirring speed) was optimized formulation based on its particle size (672.1nm), encapsulation efficiency (83.1) having higher stability of Zeta potential value of -26.2, smooth surface morphology and having higher retarded drug release with non fickkian diffusion. By studying all the characteristics it was finally concluded that a natural polymer obtained from fenugreek seed can be used as a rate controlling polymer in the preparation of nanoparticles. Keywords: Diltiazem HCl, Fenugreek seed polymer, rate controlling polymer, Nanoparticles, Desolvation.

EVALUASI IN VITRO-IN VIVO FILM TRANDERMAL DILTIAZEM HCL DENGAN PENINGKAT PENETRASI PEG 400 SEBAGAI ANTIHIPERTENSI

ABSTRACTDiltiazem HCL is an antihypertensive that low oral bioavailability of 40%, so developed to transdermal preparations. A matrix type of transdermal patch of diltiazem HCl was prepared using polyvinyl alcohol and ethyl cellulose with PEG 400 as penetration enhancer. In vitro-in vivo evaluation were conducted to asses drug permeation through the skin and determine the effectiveness of transdermal film as an antihypertensive drug. Transdermal patches of diltiazem HCl were evaluated for physicochemical characteristics weight variation, thickness, folding endurance, moisture uptake, and drug content. In vitro permeation study was conducted using commercial semi permeable membrane in Franz diffusion cell. In vivo activity study was evaluated on male rat Wistar that induced NaCl with CODA non-invasive blood pressure method. Transdermal patches of diltiazem HCl were found no significant differences in terms of physicochemical characteristics. The in vitro skin permeation profiles showed increased flux values with the increase of PEG 400 as a penetration enhancer. The in vivo evaluation showed a reduction in systolic and diastolic blood pressure within one hour after the drug administration. Diltiazem HCl was able penetration into skin, absorbed in blood circulation and effective as antihypertensive via transdermal route.Keywords : antihypertension, diltiazem HCl, PEG 400, transdermal patch

FORMULATION AND EVALUATION OF COLON TARGETED MATRIX TABLET USING NATURAL TREE GUMS

Objective: To develop a novel colon targeted tablet formulation using natural polysaccharides such as kondagogu gum and ghatti gum as carriers and diltiazem hydrochloride as a model drug.Methods: The polymer-drug tablets were prepared by wet granulation technique, coated with two layers viz., inulin as an inner coat followed by shellac as outer coat and evaluated for properties such as average weight, hardness and coat thickness. In vitro release studies of prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid (SCF) in order to mimic the conditions from mouth to colon.Results: Percentage weight variation, percent friability and content of active ingredient for all the formulations were found to be well within United States Pharmacopoeia (USP) limits. Out of both the polymers, the tablets prepared with ghatti gum showed the maximum hardness of 7.1 kg/cm2. The FTIR spectra of pure diltiazem HCl and the formulation KF3 were found to be identical. From the DSC, it was evident that the melting point peak of diltiazem HCl and formulation KF3 were observed at 217.16 and 218.34 °C respectively. In vitro studies revealed that the tablets coated with shellac (2.5% w/w), prevented the drug release in stomach environment and inulin coated tablets (4% w/w) have limited the drug release in the small intestinal environment. The data obtained from in vitro drug release studies were fit into Peppas model and in all the cases the value of A was found to be more than 2, i.e., drug release by a combination of both diffusion and erosion-controlled drug release.Conclusion: The study revealed that polysaccharides as carriers and inulin and shellac as a coating material can be used effectively for colon targeting of drugs for treating local as well as systemic disorders.