Current Issue : April - June Volume : 2021 Issue Number : 2 Articles : 5 Articles
The dissolution behavior of novel active pharmaceutical ingredients (API) is a crucial parameter in drug formulation since it frequently affects the drug release. Generally, a distinction is made between surface-reaction- and diffusion-controlled drug release. Therefore, dissolution studies such as the intrinsic dissolution test defined in the pharmacopeia have been performed for many years. In order to overcome the disadvantages of the common intrinsic dissolution test, a new experimental setup was developed within this study. Specifically, a flow channel was designed and tested for measuring the mass transfer from a flat, solid surface dissolving into a fluid flowing over the surface with well-defined flow conditions. A mathematical model was developed that distinguishes between surface-reaction- and diffusion-limited drug release based on experimental data. Three different drugs—benzocaine, theophylline and griseofulvin—were used to investigate the mass flux during dissolution due to surface reaction, diffusion and convection kinetics. This new technique shows potential to be a valuable tool for the identification of formulation strategies....
Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]·EtOH·(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics....
Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this research, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting the moisture-activated dry granulation (MADG) process. In this method, heating and drying steps were omitted so, called green granulation process. A 32 full-factorial design was performed for optimization of key process variables, namely the granulation fluid level (X1) and the wet massing time (X2). Granulation of CNG was carried out in the presence of polyvinylpyrrolidone, and the prepared granules were compressed into tablets. Regression analysis demonstrated the significant (p ≤ 0.05) effect of X1 and X2 on properties of granules and corresponding tablets, with pronounced impact of X1. Additionally, marked improvement of granules’ properties and tableting of CNG were observed. Furthermore, the optimized process conditions that produced good flow properties of granules and acceptable tablets were high level of granulation fluid (3.41% w/w) and short wet massing time (1.0 min). Finally, the MADG process gives the opportunity to ameliorate the poor flow and tableting problems of CNG with lower amounts of excipients, which are important for successful development of uniform dosage unit....
Malaria ranks amongst the major health challenges faced by many developing countries. In Sub-Saharan and tropical regions of Africa, malaria continues to claim the life of one out of every twenty children below the age of five years. In adults, mortality rates are lower, but frequent debilitating attacks reduce the quality of life for chronic sufferers. The patronage and usage of liquid herbal antimalarials in the management and treatment of malaria in Ghana have been on the ascendency over the past decade. This project seeks to transform five liquid herbal antimalarial preparations (Agbeve pevah, Time mixture, Givers mixture, Masada mixture, and Rooter mixture) produced locally and commonly used for the treatment of malaria fever into capsules. This will help eliminate the current limitations, such as lack of patient compliance due to the bitterness and bulky nature of packaged preparation. The amount of dry extract per dose of each herbal antimalarial preparation and the wavelength of maximum absorption (λmax) of aqueous solutions of Agbeve, Time, Givers, Masada, and Rooter extract were determined. The flow properties of formulated granules were determined and subsequently encapsulated. The formulated capsules were evaluated using basic pharmacopeial tests, such as uniformity of weight, disintegration, drug content, and dissolution. Difference, f1, and similarity, f2, factors were employed in analyzing the dissolution profiles of the formulated capsules. The formulated granules exhibited good flow properties and passed the weight uniformity, disintegration, and drug content tests. The capsules exhibited optimal release of extract at the 45th minute in 0.1MHCL. All formulated capsules had f 2 values >50 and f 1 values <15, indicating the similarity of their drug release profiles with their respective liquid herbal antimalarials. Oral capsules of Agbeve, Time, Givers, Masada, and Rooter have been successfully formulated and can be used as a substitute for Agbeve pevah, Time mixture, Givers mixture, Masada mixture, and Rooter mixture, respectively, in the treatment of malaria....
Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na- CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTXloaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability....
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