Dissolution Rate Of Nifedipine Research Articles

Formulation and Evaluation of Sustained Release Solid Dispersed Nifedipine Microcapsules

Conventional drug delivery system for treating the angina and hypertension are not much effective as the drug do not reach the site of action in appropriate amounts. Thus potent and guarded therapy of this angina and hypertension disorder using specific drug delivery system is a challenging task to the pharmaceutical professionals. The study was aimed at increase the solubility of poorly soluble drug nifedipine and formulating it in sustained release dosage form. Solid dispersion of drug was prepared using Poly vinyl pyrrolidone (PVP) as inert hydrophilic carriers by solvent evaporation technique. A 17-fold increase in dissolution rate of nifedipine was observed with solid dispersion prepared with PVP (K30). Sustained release microcapsules of nifedipine were formulated using Eudragit RS 100 as a polymer, acetone as polymer solvent for Eudragit RS100, N-hexane as a non-solvent, liquid paraffin vehicle, with solid dispersion of nifedipine as core by emulsion solvent evaporation method and modified emulsion solvent evaporation method. Microcapsules from all the batches were found to discrete, spherical and free flowing and % entrapment efficiency was found to be in range of 96.01% to 97.87%. All the batches of microcapsules showed sustained release curve in pH 7.4 phosphate buffer up to 12hours with maximum release up to 97.22% after 12hrs was found to be in B2. SEM studies of the microcapsules showed the surface topography states that prepared microspheres were spherical in shape. Shiny and uniform covered surface with polymer. Keywords: Nifedipine, Poly vinyl pyrrolidone, Solid dispersion, Microcapsules, Emulsion solvent evaporation method

Enhancement of Dissolution Rate and Bioavailability of Nifedipine by Chitosan Based Cocrystallization Technique

The objective of present study was to enhance solubility and dissolution behaviour of nifedipine by using cocrystallization method. A significant increase in solubility and dissolution rate of nifedipine has been demonstrated by solvent change method using chitosan. In this method, chitosan was precipitated on nifedipine crystals using sodium citrate as a salting out agent. An accurately weighed chitosan was dissolved in 1% acetic acid and drug was added in the chitosan solution. This resulting solution was added drop wise into 1% sodium citrate solution with continuous stirring. Sodium citrate precipitate polymer on drug crystals. FTIR, DSC, XRD, SEM, In-vitro dissolution studies, were studied for characterization of prepared cocrystals. Stability studies showed a good stability character of prepared cocrystals. Design Expert® software version 10.0 was used to develop polynomial models which were analysed to delineate the main effects for each CQA (critical quality attributes) through Box-Bhenken design expert. Pharmacokinetic study clearly showed the enhancement of dissolution rate of cocrystals. The above investigation concluded that the significant dose reduction is possible for nifedipine with cocrystal formulation which leads to improve patient compliance.

PREPARATION, CHARACTERIZATION AND STABILITY STUDIES OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF NIFEDIPINE

Objective: The objective of this work was to improve the solubility and dissolution rate of Nifedipine by preparing a solid-self micro emulsifying drug delivery system (Solid-smedds).
 Methods: Liquid-self-emulsifying drug delivery system formulations were prepared by using linseed oil as oil, tween 80 as a surfactant and PEG 400 as cosurfactant. Components were selected by solubility screening studies and the self-emulsifying region was identified by the pseudo-ternary phase diagram. Thermodynamic stability study was performed for the determination of stable liquid-smedds formulation. These formulations were evaluated for self-emulsification time, drug content analysis, robustness to dilution test, particle size analysis, in vitro diffusion study, and Stability study. Solid self-micro emulsifying formulations were prepared by using aerosil-200 at a different ratio. Lf9S (0.65:1) was selected due to its highest drug entrapment efficiency and a decrease in particle size. It was selected for further studies into DSC, SEM, FTIR, and XRD analysis.
 Results: DSC and XRD result shows that the drug within the formulation was in the amorphous state. From the SEM study, it was observed that the drug has been uniformly distributed and having a smooth surface. From the in vitro dissolution study, it improved the dissolution rate of nifedipine which was 98.70% of drug release where pure drug release only 6.72%.
 Conclusion: In conclusion, a solid self-micro emulsifying drug delivery system is improved the solubility and drug release rate but also improved the stability of the formulation.

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam.

This study explores the impact of paediatric patient related factors and choice of formulation on the dissolution characteristics of nifedipine and lorazepam, 2 drug substances regularly applied in very young patients and in compounded formulations. Dissolution experiments were designed to reflect clinical practice in a paediatric hospital, with respect to dosage forms, feeding regimens and methods of administration. Solubility studies addressed the influence of age and prandial state. Drug solubility and dissolution experiments were conducted in biorelevant media and adapted age-specific (neonate and infant) media. Dissolution studies were performed with the mini-paddle apparatus and the flow-through cell apparatus. Dissolution of nifedipine formulations was not affected by age-related changes of the fasted state simulated gastrointestinal fluids, and by disintegration of the formulation before administration. However, a significant difference in nifedipine's dissolution rate from commercial tablets and compounded capsules was observed. The dissolution of lorazepam tablets was affected by fasted- vs fed-state media, but it was deemed less likely to be clinically relevant. The significant effect of fed-state media on nifedipine's solubility was considered to have possible clinical relevance since very young patients are almost continuously in a fed state. The in vitro results obtained from these studies reveal the potential of biorelevant solubility and dissolution studies reflecting clinical practice to predict drug performance in paediatric patients.

Immediate-Release Nifedipine Binary Dry Powder Mixtures with Nanocellulose Featuring Enhanced Solubility and Dissolution Rate.

Nifedipine (NIF) is a 1,4-dihydropyridine-based calcium channel blocker with poor solubility, whose bioavailability is highly dependent on the type of formulation. Dry powder mixtures of 20% w/w NIF with microcrystalline cellulose (MCC) and its high surface area nanocellulose analogue, which is namely Cladophora (CLAD) cellulose, were produced by heating at the melting temperature of the drug for 1 h. Non-heated samples were used as a reference. The solid-state properties of the mixtures were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction. The drug release was studied in biorelevant media, including simulated gastric fluid (SGF), fasted-state simulated intestinal fluid (FaSIF) and fed-state simulated intestinal fluid (FeSIF). An enhanced apparent solubility and faster dissolution rate of NIF were observed in the heated mixture of NIF with CLAD-H in all tested biorelevant media (i.e., SGF, FaSIF and FeSIF), which was due to NIF amorphization in the high surface area nanocellulose powder. Ordinary MCC, which is essentially non-porous, did not produce an enhancement of a similar magnitude. The results of the study suggest that dry powder formulation using high surface area nanocellulose is a facile new strategy for formulating calcium channel blocker drugs, which could potentially be a viable alternative to currently used soft gel liquid capsules.

Role of Co-Processed Superdisintegrants in Enhancing the Dissolution Rate of Nifedipine in Sublingual Tablets

Role of Co-Processed Superdisintegrants in Enhancing the Dissolution Rate of Nifedipine in Sublingual Tablets

Mechanism of Enhanced Nifedipine Dissolution by Polymer-Blended Solid Dispersion through Molecular-Level Characterization.

We investigated the effect of polymer composition on nifedipine (NIF) dissolution through molecular-level characterization of NIF/hypromellose (HPMC)/Eudragit S (EUD-S) ternary solid dispersions. The dissolution rates and molecular states of NIF and polymers were evaluated in NIF/HPMC/EUD-S spray-dried samples (SPDs) with different polymer compositions. Blending of HPMC and EUD-S improved the dissolution property of each polymer. Moreover, polymer blending enhanced NIF dissolution from the NIF/polymer SPD with EUD-S/polymer wt % of 50-75%. NIF dissolved simultaneously with polymers from the NIF/polymer SPDs with high EUD-S/polymer wt %. In contrast, NIF and polymers separately dissolved from the NIF/polymer SPDs with EUD-S/polymer wt % of 10-25%, exhibiting a significantly reduced NIF dissolution rate. Fourier transform-infrared and solid-state NMR measurements revealed that HPMC and EUD-S formed molecular interactions with NIF via different interaction modes. Comprehensive analysis by spectroscopic measurements and modulated differential scanning calorimetry showed that the molecular interaction between NIF and EUD-S was stronger than that between NIF and HPMC. Furthermore, the 13C-spin-lattice relaxation time measurements revealed that EUD-S effectively restricted the molecular mobility of NIF compared with HPMC. The molecular interaction between NIF and EUD-S led to the simultaneous and fast dissolution of NIF with EUD-S from the NIF/polymer SPD with high EUD-S loading. Thus, enhanced NIF dissolution was ascribed to the fast dissolution properties of the blended polymer and to polymer-controlled NIF dissolution through the strong molecular interaction between NIF and EUD-S. To achieve efficient optimization of the formulation of polymer-blended solid dispersion with desired drug dissolution, it is necessary to consider both polymer-polymer and drug-polymer intermolecular interactions.

Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization

Purpose: To evaluate the physicochemical and in vitro characteristics of solid dispersions using BCS II model drugs with Soluplus® and one of its component homopolymers, PEG 6000. Methods: Nifedipine (NIF) and sulfamethoxazole (SMX) of 99.3% and 99.5% purity, respectively, were selected as BCS II model drugs, such that an improved dissolution rate and concentration in the gastrointestinal tract should increase oral bioavailability. Soluplus® is an amorphous, tri-block, graft co-polymer with polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol (PCL:PVAc:PEG6000) in the ratio 57:30:13. PEG 6000 (BASF) is a waxy material with melting point of about 60°C. Solid dispersions were prepared using lyophilization or spray drying techniques. Dissolution study, crystallinity content, and analysis for new chemical bond formation have been used to evaluate the dispersed materials. Results: Although each polymer improved the drug dissolution rate, dissolution from Soluplus® was slower. Enhanced dissolution rates were observed with NIF solid dispersions, but the dissolution profiles were quite different due to the selected technique, polymer, and dissolution medium. For SMX, there was similarity across the dissolution profiles despite the medium, polymer, or applied technique. Each polymer was able to maintain an elevated drug concentration over the three hour duration of the dissolution profile, i.e., supersaturation was supported by the polymer. DSC thermograms revealed no melting endotherm, suggesting that the drug is amorphous or molecularly dispersed. Conclusion: NIF and SMX solid dispersions were successfully prepared by spray drying and lyophilization using Soluplus® or PEG 6000. Each polymer enhanced the drug dissolution rate; NIF dissolution rate was improved to a greater extent. Dispersions with PEG 6000 had a faster dissolution rate due to its hydrophilic nature. DSC analysis showed that no crystalline material exists in the dispersions.

Dissolution enhancement of the poorly soluble drug nifedipine by co-spray drying with microporous zeolite beta

Dissolution enhancement of nifedipine (NIF), a BSC class II drug, was achieved after co-spray drying with zeolite beta (BEA) in two drug to carrier ratios (1: 1, 1: 2). Extraction studies revealed almost 100% encapsulation efficiency. Physisorption studies suggested successful drug incorporation within the carrier's pore network, as well as on its external surface area. A shift of ζ-potential towards less negative values following drug loading indicated possible drug deposition onto zeolite's surface. The physical state of loaded NIF was evaluated by means of FT-IR, DSC and XRD analyses, all corroborating towards drug's significant amorphization.The in vitro dissolution rate of NIF from the co-spray dried formulations was substantially enhanced in simulated gastric (pH 1.2) and intestinal fluids (pH 6.8), compared to crystalline drug.Results demonstrated the potential of zeolitic particles for the dissolution enhancement of sparingly soluble drugs, which in turn may increase their oral bioavailability.

The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement

The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used.

Manufacture of Ternary Solid Dispersions Composed of Nifedipine, Eudragit<sup>®</sup> E and Adsorbent

The aim of this study was to manufacture the ternary solid dispersions composed of nifedipine, Eudragit® E and adsorbent. Dissolution enhancement of nifedipine was also investigated. The inert solid carriers were added in the mixtures of nifedipine and Eudragit® E at varying ratios. The physicochemical properties of ternary systems, compared to physical mixtures, were analyzed using powder x-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The dissolution of nifedipine from ternary systems was compared to the drug alone. The influence of drug:polymer: adsorbent ratio and type of adsorbent on the dissolution rate of the drug was also evaluated. The PXRD and DSC results of the systems with high amount of polymer showed that the drug was present in an amorphous form. On the other hand, the diffraction patterns and DSC thermograms of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The results from this study demonstrated that an improvement in dissolution rate of nifedipine with Eudragit® E and adsorbents was obtained.

Development and evaluation of nifedipine controlled release tablets prepared using mucoadhesive swellable polymer

Nifedipine is embedded in Gelcarin GP-379 to develop a prolonged release matrix. The effect of polymers levels (15, 20, 30 and 50% w/w), diluent type (lactose Fast Flo, DiTab, and Avicel PH-101), and drug levels (13, 20 and 30% w/w) on in vitro release rate of the drug were investigated. The formulation containing 13% nifedipine, 20% Gelcarin GP-379, and lactose Fast Flo controlled the dissolution rate of nifedipine and released approximately 51% drug at 8 h of testing dissolution. The use of different types of diluents, different drug levels, and different rotational speeds during dissolution testing did affect the drug release rate from the swellable matrices. The dissolution data were analyzed according to Higuchi model, zero order, first order, and Peppas kinetic model. Drug release was found to follow the anomalous diffusion model for swellable matrix.

Characterization and physical stability of fast-dissolving microparticles containing nifedipine

The suitability of a poly(sodium methacrylate, methyl methacrylate) (NaPMM), a novel mucoadhesive material, to prepare fast-dissolving microparticles containing nifedipine (NIF) in the range of 25–75% w/w was verified. Microparticles made of a low-viscosity hydroxypropylmethylcellulose (HPMC), were also prepared to compare the NIF release profile and bioadhesive properties. The release test was carried out in oversaturation conditions. The physical state of microparticles was also investigated. The formulation stability was evaluated over a 3-month period in long-term and accelerated conditions. The presence of amorphous NIF within freshly prepared microparticles was attributed to interactions between the drug and both polymers. NaPMM conferred to microparticles suitable mucoadhesive properties and significantly increased NIF dissolution rate in comparison to HPMC. Nevertheless, NIF apparent solubilities obtained by NaPMM microparticles were lower than those obtained by the HPMC set. After 3-month storage in the case of HPMC microparticles, NIF dissolution rate and supersaturation degree significantly decreased due to drug crystallization. As far as NaPMM microparticles are concerned, neither NIF dissolution rate nor apparent solubility significantly changed.

Nanoparticle Multilayers: Surface Modification of Photosensitive Drug Microparticles for Increased Stability and In Vitro Bioavailability

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.

Physical properties and dissolution behaviour of nifedipine/mannitol solid dispersions prepared by hot melt method

Solid dispersions of nifedipine (NIF) with mannitol in preparations containing 10 and 50% (w/w) of drug were manufactured by the hot melt method. Physical properties and the dissolution behaviour of binary systems as physical mixtures and solid dispersions were investigated. In all samples, the crystal structure of NIF was confirmed using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) revealed, there was no interaction between drug and carrier, however, FTIR spectra indicated formation of thermodynamically less stable polymorph of mannitol. The dissolution rate of NIF from solid dispersions was markedly enhanced, the effect being stronger at higher drug loading (50%, w/w, NIF). The dissolution rate enhancement was attributed to improved wetting of NIF crystals due to mannitol particles, attached on the surface, as inspected by means of SEM. Thermal stability of NIF, mannitol and two other potential carbohydrate carriers (lactose and saccharose) during the hot melt procedure was investigated using 1H NMR. NIF was found to be thermically stable under conditions applied. As expected, among carriers only mannitol demonstrated suitable resistance to high temperature used in experiments.

Characterization of nifedipine solid dispersions.

The sublingual administration of nifedipine (NIF) is currently used in clinical practice. The sublingual administration of NIF solid dispersions (SD), by using a suitable dispenser, appears an interesting approach in the treatment of moderate and severe hypertensive emergencies. With this aim nine SD made of NIF and a low viscosity hydroxypropylmethylcellulose (HPMC) in different ratio were prepared by means of spray-drying technique and their structure was studied. Moreover, the drug dissolution properties from SD were verified. The characteristic peaks of crystalline NIF were not detectable by using the X-ray analysis when the NIF/HPMC ratios were lower than 50/50 w/w. In thermograms obtained from SD, the NIF melting endothermic peak disappeared when NIF/HPMC ratios were lower than 30/70 w/w; the experimental Tg values of SD were lower than the Tg values predicted by Gordon Taylor equation suggesting some type of non-ideality of mixing. In the SD FTIR spectra the NH stretching vibrations and the C=O stretch in esteric groups of NIF shift to free NH and C=O regions indicating the rupture of intermolecular hydrogen bond in the crystalline structure of NIF. The prepared SD improved the NIF dissolution rate in comparison with that of commercial NIF or NIF/HPMC physical mixtures. Moreover, the concentration of NIF in the dissolution medium increased decreasing the NIF content.

Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone.

We attempted the development of rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The co-ground mixture was prepared with a vibration rod mill. The tablets were formed by compression using a single punch-tableting machine after addition of the co-ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate. Regarding the properties of tablets, hardness and the time of disintegration were measured. The particle diameter and specific surface area of the co-ground mixture were measured. The tablets manufactured from a physical mixture of 30% (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with 65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s. We found that adding co-ground mixture of D-mannitol and crospovidone is useful in enhancing hardness of the tablets that could not be achieved by addition of their individually ground mixture. The improvement in the hardness of the tablets was also observed when other saccharides and disintegrants were used. This method was proved to be applicable in the manufacture of tables of ascorbic acid, a water-soluble drug and nifedipine, a slightly water soluble drug; and the dissolution rate of nifedipine from the tablets in water was remarkably improved. The particle sizes of D-mannitol in the co-ground mixture were smaller than that of the individually ground mixture, resulting in a larger specific surface area of the co-ground mixture than that of the individually ground mixture. Therefore, it was presumed that crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.

Influence of pluronic F-68 on dissolution and bioavailability characteristics of multiple-layer pellets of nifedipine for controlled release delivery

A multiple-layer design of pellets for nifedipine was developed using pluronic F-68 to enhance dissolution rate. The influence of ratios of nifedipine in the inner layer to that in the outer layer, the ratios of pluronic F-68 to nifedipine in the solid dispersion, and the thickness of the control membrane on dissolution characteristics were investigated. With an increasing ratio of pluronic F-68 to nifedipine, the dissolution rate of nifedipine was gradually promoted and the extent of release was enhanced as well. DSC thermograms illustrate the gradual disappearance or broadening of the nifedipine melting peak with the presence of pluronic F-68. The decrease of the nifedipine ratio in the inner layer and the increase of the ratio of pluronic F-68 to nifedipine in the outer layer can enhance the release of nifedipine. With a fixed nifedipine ratio of 1.5 between the inner layer and the outer layer, increasing the ratio of pluronic F-68 to nifedipine in the outer layer significantly increased the initial release rate of nifedipine. By increasing the nifedipine ratio of the inner layer to the outer layer to 1:1, the increase of coating percentage referenced to the total weight decreased the release rate of nifedipine from the inner layer. The pharmacokinetic bioequivalence between the test product (Cardilate, N-6) and Coracten was found with a multiple-dose oral administration of 20 mg in 12 healthy, normal Chinese male volunteers.

Investigation of Dissolution Enhancement of Nifedipine by Deposition on Superdisintegrants

In this study we aimed to investigate the dissolution enhancement of nifedipine by the solvent deposition technique using superdisintegrants including Ac-Di-Sol, Kollldon CL, and Explotab as excipients. The relative significance of action of solvent deposition (deposition of small drug particles on the excipient after solvent is evaporated) and action of superdislntegrant was investigated. The effect of solvent on dissolution of nifedipine in the solvent deposition system was also Investigated. Differential scanning calorlmetry (DSC) was used to study the interaction between nifedipine and superdisintegrants. Capsules and tablets of a physical mixture and a solvent deposition system of nifedipine were prepared. The dissolution rate of nifedipine of these capsules and tablets was studied. The results of this study show that solvent deposition system with lactose and super dlslntegrants in capsule and tablet dosage forms can significantly enhance dissolution rate of nifedipine. Both the action of superdislntegrant and solvent deposition contribute to the enhancement of the dissolution, but the solvent deposition is mainly responsible for this enhancement. The solvent and disintegrants used can influence the dissolution rate also. The solvent deposition system using both Kollldon CL as excipient and dichloromethane as solvent has the highest dissolution rate. DSC study indicated Kollldon CL has the strongest interaction with nifedipine also.

Effect of particle size on the available surface area of nifedipine from nifedipine-polyethylene glycol 6000 solid dispersions

Solid dispersions containing 5%, 10%, 20%, 30% and 50% of nifedipine were prepared with polyethylene glycol (PEG) 6000 as carrier, respectively, by the fusion method. Drug release from four different size fractions of nifedipine-polyethylene glycol 6000 solid dispersions were examined. The probability parameters of Weibull distribution or log-normal distribution could be obtained from linear regression of the dissolution data. The effects of particle size on the dissolution rate of nifedipine were evaluated in terms of the time course of the available surface area (S(t)). The X-ray diffraction patterns showed that nifedipine was dispersed homogeneously in an amorphous state in the solid dispersions with nifedipine concentration up to 10%. The initial values and faster rate of decrease of S(t) during the dissolution process were markedly enhanced in the solid dispersions with lower contents of nifedipine (5% and 10%) due to the formation of high energy metastable (amorphous) states of the drug and differences in the particle sizes had little effect on the values of the available surface area and the dissolution of the drug. Values of available surface area were particle size dependent for the solid dispersions with higher contents of nifedipine (20%, 30% and 50%) and the rate of decrease of S(t) was enhanced as the particle size reduced.