pH-independent Release Profiles Research Articles

Formulation, Optimization and Evaluation of Solid SMEDDS of Pioglitazone

This investigation assessed 32 formulations of liquid self-microemulsifying drug delivery system (L-SMEDDS) for pioglitazone (PGZ). The optimal PLS12 formulation comprises 40% capmul MC8 (oil), 40% cremophore RH40 (surfactant), and 20% PEG (co-surfactant). PLS12 exhibited approximately 75 nm droplet size, below 200 nm, and a PDI of 0.47, indicating nanosized droplets with uniform distribution. The formulation demonstrated stability, and achieved supreme drug loading capacity. The enhanced L-SMEDDS was solidified into solidified SMEDDS utilizing Sylloid 244 FP, subsequently in a free-flowing powder without drug interactions. Tablets were successfully formulated by incorporating S-SMEDDS with diverse tableting excipients. The selected tablet batch passed quality control and stability tests. The tablet exhibited a rapid and pH-independent release profile. The combined impact of SMEDDS and tablets collectively enhanced the solubility and dissolution of PGZ hydrochloride

Evaluation of self-nanoemulsifying drug delivery systems using multivariate methods to optimize permeability of captopril oral films

The present report demonstrates a quality by design approach to understand and optimize self-nanoemulsifying orodispersible films (SNEODF) of captopril for hypertension. A central composite experimental design was used to study the formulation parameters effects (primary emulsion, aqueous phase, and surfactant) on the film properties (globule size, film burst, adhesion, Young's moduli, disintegration time, tensile strength and dissolution). Principle component analysis (PCA) and principle component regression (PCR) were employed to identify and quantify the effects of formulation variables and physico-mechanical properties of the film on the drug permeability. PCA classified three distinct groups of film formulations based on their composition and properties. PCR quantified the impact of main variables, their interactions, and square effects on the drug permeability. The main effect of the aqueous phase exhibited a negative impact, while that of flux and tensile strength showed a positive impact on the permeability. Interactions of primary emulsions with disintegration time and tensile strength displayed a synergistic impact. Interactions of aqueous phase with flux, Young's moduli, and tensile strength, as well as between Young's moduli and tensile strength showed a significant positive effect on the permeability. A negative correlation of square effects of primary emulsion and flux, and a positive square effect of Young's moduli confirmed their non-linear influence on the drug permeability across porcine buccal mucosa. This research work demonstrates application of design of experiment and multivariate methods to achieve targeted product quality of captopril (SNEODF) having improved permeability and pH independent release profile.

Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug

The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH6.8 and pH1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24h in acidic media (pH1.2). The release profile in acidic media was similar to the alkaline media (pH6.8) with a similarity factor (f2) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.

Preparation and characterization of liquisolid compacts for improved dissolution of telmisartan.

The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement (P < 0.005) in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months.

Monitoring of internal pH gradients within multi-layer tablets by optical methods and EPR imaging

The high variability of gastrointestinal pH is a general challenge regarding constant release from oral drug delivery systems, especially for ionisable drugs. These drugs often show a pH-dependent solubility and therewith associated intra- and inter-individual variability of emerging drug plasma levels. Several strategies have been investigated with the intention to influence the microenvironmental pH (pH M) within solid formulations and therefore achieve pH-independent release profiles. Because of the heterogeneity of solid systems, a precise prediction of the occurring pH M is rather difficult. It is therefore important to monitor the pH M within the formulations to achieve requested release as well as to minimise pH-dependent degradation processes of the active compound. The purpose of the current study was the analysis of pH M gradients within 2- and 3-layer tablets during hydration using 3 different techniques for comparison intensions, in particular a pH indicator dye, fluorescence imaging and EPR imaging. The influence of the presence or absence of pH modifying substances and of an additional lipophilic inter layer on the pH M was investigated as well as the variation of matrix forming excipient and buffer pH. The influence of the pH M on drug release was analysed as well. In addition, benchtop MRI was accomplished to gain a deeper insight on the hydration and erosion behaviour of 2- and 3-layer tablets.

Modulating pH-independent release from coated pellets: Effect of coating composition on solubilization processes and drug release

The aim of the study was to clarify the influences of three coating parameters on the drug release from chlorpheniramine maleate (CPM) pellets, coated with blends of poly(vinyl acetate) (PVAc) and poly(vinyl alcohol)–poly(ethylene glycol) (PVA–PEG) graft copolymer. A central composite design was implemented to investigate the effect of the polymer blend ratio, the film coat thickness and the plasticizer concentration on the drug release. The solubilization inside the pellets was monitored by EPR spectroscopy. The blending ratio of both the polymers and the film thickness were found to have a major influence on the drug release and the solubilization speed, in contrast to the plasticizer concentration. A pH-independent release profile was adjustable via modulating the polymer blend ratio and the coating thickness. A mathematical model was developed, providing a good predictability of the release profile, based on the film coat composition. This model offers the possibility to achieve a defined drug-release profile by selective adaptation of the film coat composition, in view of process times, feasibility or polymer costs.

Preparation of an extended-release matrix tablet using chitosan/Carbopol interpolymer complex

A chitosan and Carbopol interpolymer complex (IPC) was formed using a precipitation method in an acidic solution. The chitosan and Carbopol IPC was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and turbidity measurements. FT-IR demonstrated that the IPC formed a complex through an electrostatic interaction between the protonated amine (NH 3 +) group of chitosan and the carboxylate (COO −) group of Carbopol. DSC indicated the IPC to have different thermal characteristics from chitosan or Carbopol. The turbidity measurement revealed the complexation ratio of IPC between chitosan/Carbopol to be 1/4. A theophylline tablet was prepared using the IPC as a matrix material. The drug release profile from this tablet was similar to that from the HPMC tablet and showed a pH-independent release profile. The mechanisms for drug release from the IPC tablet were diffusional release at pH 6.8 and relaxational release at pH 1.2.

PH-independent release of a basic drug from pellets coated with the extended release polymer dispersion Kollicoat ® SR 30 D and the enteric polymer dispersion Kollicoat ® MAE 30 DP

The objective of this study was to obtain pH-independent release profiles from coated pellets containing drugs with pH-dependent solubility. pH-independent release of the basic model drug verapamil HCl was achieved by coating with a combination of the neutral polymer dispersions Kollicoat ® SR 30 D (aqueous dispersion of polyvinyl acetate) and the enteric polymer dispersion Kollicoat ® MAE 30 DP (aqueous dispersion of methacrylic acid and ethyl acrylate copolymer; methacrylic acid copolymer type C). The two polymers where applied either as separate layers (enteric polymer+extended release polymer or vice versa) or as a polymer blend. A careful balance of the ratios of the polymers allowed the achievement of a pH-independent release. Higher amounts of the enteric polymer in the polymer blend resulted in a reversal of the pH-dependency, e.g. a faster release at pH 6.8 than in 0.1 N HCl.

실리마린의 용출개선 및 흰쥐에서의 생체이용률 평가

Silybin is the main component of Cardus marianus extracts originated from Silybum marianum and has a hepato-protective effect. It is a water-insoluble compound and poorly absorbed from the gastrointestinal tract, resulting in very low oral bioavailability(BA). Polymeric mixed-micelle precursor formulation was made to enhance the dissolution rate of silybin, showing the results of pH-independent release profile with increased dissolution. Oral BA of different preparations in rats was evaluated, revealing that the new formulation showed increased BA more than 2-fold and 4-fold compared to the marketed product and Cardus marianus extracts itself, respectively.

Ibuprofen release kinetics from controlled-release tablets granulated with aqueous polymeric dispersion of ethylcellulose II: Influence of several parameters and coexcipients

The objective of this study was to investigate the mechanism of ibuprofen (IBF) release from tablets prepared by wet granulation method, using Surelease as a granulating agent. The influence of certain parameters such as the levels of Surelease solids content (SSC), pH of dissolution media, selected dissolution method, and agitation speed on the release profiles of IBF was investigated. The effect of partial replacement of lactose (primary excipient) by various coexcipients such as microcrystalline cellulose, starch, polyvinylpyrrolidone (PVP), sodium alginate, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethyl cellulose (CMC–Na) was also studied. Tablets prepared with surelease as a granulating agent were non-disintegrating and exhibited prolonged release rates as compared to control tablets. The release of IBF from the tablets appears to occur either via water-filled pores or by diffusion through membrane, depending on the levels of SSC. At higher SSC levels pH independent release profiles for IBF were achieved. Dissolution method and agitation speed exhibited no significant effect on the release profiles. All the coexcipients studied enhanced the release rates, irrespective of whether the coexcipients were water-soluble or water-insoluble.

On the employment of λ carrageenan in a matrix system. III. Optimization of a λ carrageenan–HPMC hydrophilic matrix

The λ carrageenan/HPMC ratio in matrix tablets has been optimized in order to obtain pH-independent release profiles of chlorpheniramine maleate, a freely soluble drug. Release profiles in acidic (pH 1.2) and neutral (pH 6.8) media were fitted according to the Weibull and the power law models. Model independent parameters ( t 50% and the percentage of drug released after 2 h) were also calculated. The Weibull parameters were found suitable to describe the dependence of the release profiles on matrix composition. Preparation and testing of the optimized formulation showed linear and pH-independent release profiles lasting about 24 h, in good accordance with the values predicted by the optimization procedure.

The influence of polymeric excipients on drug release from hydroxypropylmethylcellulose matrices

The effect of various polymers and ion-exchange resins on drug release from hydroxypropylmethylcellulose (HPMC) matrices has been evaluated. Non-ionic polmers did not significantly alter release rates. Ionic polymers, however, were capable of retarding the release of oppositely charged molecules, but the effect was small. Ion-exchange resins had a profound effect. It is believed that, provided the drug and the resin are oppositely charged, they will bind together in situ within the HPMC matrix, leading to reduced drug release rates. The drug is liberated once sufficient ions are available to displace it from the binding site. It was not surprising, therefore, to find that the ionic strength of the dissolution fluid affected the action of the resin. Nevertheless, the HPMC matrix was shown to have an inherent buffering capacity, which allowed a virtually pH independent release profile to be obtained.