Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Tekućinsko-čvrsti pripravci kao sredstvo za evaluaciju i poboljšanje fizičkokemijskih svojstava teško topljivih lijekova

The potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (indomethacin) was investigated. In this study, different formulations of liquisolid tablets using different co-solvents (non-volatile solvents) were prepared and the effect of aging on the dissolution behaviour of indomethacin liquisolid compacts was investigated. To evaluate any interaction between indomethacin and the other components in liquisolid formulations, X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) were used. Dissolution test was carried out at two different pH, 1.2 and 7.2, to simulate the stomach or intestine fluid, respectively. The results showed that liquisolid formulations exhibited significantly higher drug dissolution rates at pH 1.2 and 7.2 compared to compacts prepared by the direct compression technique. The enhanced rate of indomethacin dissolution from liquisolid tablets was, due to an increase in wetting properties and surface area of drug particles available for dissolution. In order to investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the formulations were stored at 25 oC/75% relative humidity for a period of 12 months. The results showed that aging had no significant effect on dissolution profiles of liquisolid tablets. Liquisolid compacts containing propylene glycol as vehicle produced higher dissolution rates in comparison with liquisolid compacts containing PEG 400 or Tween 80 of the same concentration. The DSC and XPD results showed no changes in crystallinity of the drug and interaction between indomethacin and excipients (Avicel and silica) during the process.U radu je ispitivan učinak tekućinsko-čvrstih sustava na poboljšanje oslobađanja u vodi netopljivih tvari (indometacina). Koristeći različita nehlapljiva otapala pripravljeno je nekoliko tekućinsko-čvrstih tableta, a zatim je proučavan učinak starenja na oslobađanje indometacina. Moguće interakcije između indometacina i drugih komponenata praćene su difrakcijom rentgenskih zraka na praškastom uzorku (XPD) i diferencijalnom pretražnom kalorimetrijom (DSC). Oslobađanje je praćeno pri dva različita pH, 1,2 i 7,2, simulirajući uvjete u želučanoj ili crijevnoj tekućini. Rezultati pokazuju da je profil oslobađanja iz tekućinsko-čvrstih pripravaka značajno bolji pri pH 1,2 ili 7,2, u usporedbi s pripravcima dobivenim kompresijom. Poboljšanje oslobađanja indometacina iz tekućinsko-čvrstih pripravaka posljedica je povećanog vlaženja površine čestica ljekovite tvari. Da bi se proučio učinak starenja na čvrstoću pripravaka i oslobađanje ljekovite tvari, tekućinsko-čvrsti pripravci su uskladišteni 12 mjeseci na 25 oC/75% relativne vlažnosti. Rezultati ukazuju da starenje nema značajni učinak na profil oslobađanja. Pripravci s propilenglikolom imaju bolji profil oslobađanja nego pripravci s istom koncentracijom PEG 400 ili Tween 80. DSC i XPD pokazuju da nije došlo do promjene kristaliničnosti niti do interakcije između indometacina i pomoćnih tvari (Avicel i silikagel) za vrijeme izrade pripravaka

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

ABSTRACT The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Factors affecting the morphology of benzoyl peroxide microsponges

Benzoyl peroxide (BPO) is primarily used in the treatment of mild to moderate acne. However, its application is associated with skin irritation. It has been shown that encapsulation and controlled release of BPO could reduce the side effect while also reducing percutaneous absorption when administered to the skin. The aim of the present investigation was to design and formulate an appropriate encapsulated form of BPO, using microsponge technology, and explore the parameters affecting the morphology and other characteristics of the resultant products employing scanning electron microscopy (SEM). Benzoyl peroxide particles were prepared using an emulsion solvent diffusion method by adding an organic internal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane into a stirred aqueous phase containing polyvinyl alcohol (PVA). Different concentrations of BPO microsponges were incorporated in lotion formulations and the drug release from these formulations were studied. The SEM micrographs of the BPO microsponges enabled measurement of their size and showed that they were spherical and porous. Results showed that the morphology and particle size of microsponges were affected by drug:polymer ratio, stirring rate and the amount of emulsifier used. The results obtained also showed that an increase in the ratio of drug:polymer resulted in a reduction in the release rate of BPO from the microsponges. The release data showed that the highest and the lowest release rates were obtained from lotions containing plain BPO particles and BPO microsponges with the drug:polymer ratio of 13:1, respectively. The kinetics of release study showed that the release data followed Peppas model and the main mechanism of drug release from BPO microsponges was diffusion

Factors affecting the morphology of benzoyl peroxide microsponges

Benzoyl peroxide (BPO) is primarily used in the treatment of mild to moderate acne. However, its application is associated with skin irritation. It has been shown that encapsulation and controlled release of BPO could reduce the side effect while also reducing percutaneous absorption when administered to the skin. The aim of the present investigation was to design and formulate an appropriate encapsulated form of BPO, using microsponge technology, and explore the parameters affecting the morphology and other characteristics of the resultant products employing scanning electron microscopy (SEM). Benzoyl peroxide particles were prepared using an emulsion solvent diffusion method by adding an organic internal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane into a stirred aqueous phase containing polyvinyl alcohol (PVA). Different concentrations of BPO microsponges were incorporated in lotion formulations and the drug release from these formulations were studied. The SEM micrographs of the BPO microsponges enabled measurement of their size and showed that they were spherical and porous. Results showed that the morphology and particle size of microsponges were affected by drug:polymer ratio, stirring rate and the amount of emulsifier used. The results obtained also showed that an increase in the ratio of drug:polymer resulted in a reduction in the release rate of BPO from the microsponges. The release data showed that the highest and the lowest release rates were obtained from lotions containing plain BPO particles and BPO microsponges with the drug:polymer ratio of 13:1, respectively. The kinetics of release study showed that the release data followed Peppas model and the main mechanism of drug release from BPO microsponges was diffusion

Enhancement of dissolution rate of piroxicam using liquisolid compacts

Piroxicam is a poorly soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. There are several techniques to enhance the dissolution of poorly soluble drugs. Among them, the technique of liquisolid compacts is a promising technique towards such a novel aim. In this study, the dissolution behaviour of piroxicam from liquisolid compacts was investigated in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). To this end, several liquisolid tablets formulations containing various ratios of drug:Tween 80 (ranging from 10% to 50% w/w) were prepared. The ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was kept constant in all formulations. The results showed that liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made (capsules and directly compressed tablets containing micronized piroxicam). This was due to an increase in wetting properties and surface of drug available for dissolution

The Effect of Type and Concentration of Vehicles on the Dissolution Rate of a Poorly Soluble Drug (indomethacin) from Liquisolid Compacts

PURPOSE: For poorly soluble, highly permeable (Class II) drugs, such as indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. The object of the present study is to increase dissolution rate of indomethacin using liquisolid compacts. METHODS: Several formulations of liquisolid compacts containing various ratios of drug: propylene glycol (ranging from 1:1 to 1:4) was prepared. In this study the ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was 20 in all formulations. The dissolution behaviour of indomethacin from liquisolid compacts and conventional formulations was investigated at different pHs (1.2 and 7.2). RESULTS: The results showed that liquisolid compacts demonstrated considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets containing indomethacin. This was due to increased wetting properties and surface of drug available for dissolution. Also it has been shown that the fraction of molecularly dispersed drug (FM) in the liquid medication of liquisolid systems was directly proportional to their indomethacin dissolution rates (DR). An attempt was made to correlate the percentage drug dissolved in 10-min with the solubility of indomethacin in different vehicles. A plot of the percentage drug dissolved against the solubility of indomethacin showed that the amount of drug dissolved increased linearly (correlation coefficient of 0.9994 and 0.996 at pH 7.2 and 1.2 respectively) with an increase in solubility of indomethacin in the vehicles. CONCLUSION: The liquisolid compacts technique can be a promising alternative for the formulation of water insoluble drugs, such as indomethacin into rapid release tablets

Filgrastim (G-CSF) loaded liposomes: mathematical modeling and optimization of encapsulation efficiency and particle size

Introduction: Optimization of filgrastim (G-CSF) (granulocyte colony stimulating factor) liposomes formulation prepared by the method of film hydration was the aim of this research. Methods: To study the independent variables effects in the development of filgrastim (G-CSF) liposomes, method of factorial design was applied. The molar ratio of dipalmitoyl phophatidylcholine (DPPC) per cholesterol (Chol.) and hydration time were chosen as two independent factors. The dependent variables were encapsulation efficiency percent (EE %) and particle size (PS). Ultrafiltration method was applied for separation of un-encapsulated protein. RP-HPLC method was employed for analysis of G-CSF. Results: Application of response surface methodology (RSM) in formulation of filgrastim liposomes and the obtained results for responses including particle size and EE % showed that the main effective independent variable was DPPC/Chol molar ratio. Different impacts of influencing parameters including interaction and individual effects were checked employing a mathematical method for obtaining desired liposomes. Optimum liposomal formulations were established using this method for enhancing their characteristics. Average percent errors (APEs) were 3.86% and 3.27% for predicting EE % and PS, respectively which reflect high model ability in this regard. Conclusion: It is concluded that observed and predicted values regarding PS and EE % were consistent and this model is efficient enough in prediction of the mentioned characteristics while preparing filgrastim (G-CSF) liposomes

An Investigation on Physicochemical Properties of Piroxicam Liquisolid Compacts

The potential of liquisolid systems to improve the dissolution properties of water-insoluble agent (piroxicam) was investigated. In this study, physicochemical properties of piroxicam liquisolid tablets, effect of aging and type of the carrier was also investigated. To this end, several liquisolid tablets formulations containing various ratios of drug: solvent and different carriers were prepared. X-ray crystallography, differential scanning calorimetry (DSC) and contact angle measurement were used for evaluation of physicochemical properties of piroxicam. Liquisolid compacts exhibited significantly higher drug dissolution rates, in different dissolution media, compared to compacts prepared by the direct compression technique. The results showed that enhanced dissolution rate of piroxicam liquisolid tablets was due to an increase in wetting properties and surface area of drug available for dissolution. In order to investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the cformulations were stored at 25oC/75% relative humidity for a period of 9 months. The results showed that aging had no significant effect on hardness or dissolution profile of liquisolid tablets. It was shown that Avicel had more liquid retention potential in comparison with other carriers, but there were no significant differences in the dissolution profiles between formulations. The results of DSC and X-ray crystallography did not show any changes in crystallinity of the drug and interaction between piroxicam and exipients (Avicel and silica) during the process