ABSTRACT
Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
ABSTRACT
Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
ABSTRACT
OBJECTIVE:To prepare total flavonoids of Hippophae rhamnoides(TFH)-PVP K30 solid dispersion,and to char-acterize and study its in vitro dissolution. METHODS:Solvent method was used to prepare TFH-PVP K30 solid dispersion with dif-ferent drug-loading ratio of 1:1,1:2,1:3,1:4,1:5;single factor test was designed to screen drug-loading ratio using dissolution parameter Td as index;orthogonal test was designed to optimize ultrasonic time,temperature of water bath and drying time for prep-aration technology using in vitro dissolution rate as index,and then validated. SEM,DSC and FT-IR were used to characterize sol-id dispersion. RESULTS:Td of TFH-PVP K30 solid dispersion was the lowest when drug-loading ratio was 1:3. Optimal technolo-gy was ultrasonic time 10 min,temperature of water bath 60 ℃ and drying time 12 h. 90 min accumulative dissolution rate of pre-pared TFH-PVP K30 solid dispersion was 90.22% in average(RSD=1.74%,n=3). The results of SEM,DSC and FT-IR showed that the drug as amorphous form dispersed in the PVP K30,the formation of hydrogen bond of the both. CONCLUSIONS:TFH-PVP K30 solid dispersion is prepared successfully,and in vitro dissolution rate of it is improved significantly.
ABSTRACT
The aim of present study was to improve dissolution rate of olanzapine by means of solid dispersion using combination of hydrophilic polymer (PEG & PVP) by using response surface design. Solid dispersion containing olanzapine were prepared using PEG 20000 & PVP K 30 by melted fusion method. Response surface method was used for the optimization olanzapine solid dispersions. Amount of PEG 20000 and Amount of PVP K 30 were selected as the critical process parameters (Independent variable) whereas amount dissolved in 10 minute (Q 10) and amount dissolved in 45 minute (Q 45) were selected as critical quality attributes (dependent variables). Optimized solid dispersion batch was characterized using infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry (XRD).Dissolution studies indicated a significant improvement in dissolution of olanzapine when dispersed in PEG 20000 and PVP k 30. XRD and DSC study indicated amorphous form of prepared solid dispersions. On the basis of numerical optimization technique, PEG 20000(X1) and amount of PVP K 30(X2) were 11.20 % and 14.53 % in optimized solid dispersion. The observed responses were closed well with the predicted values. The response surface method is found to be robust and accurate for optimization of solid dispersion for increase in solubility and dissolution rate of olanzapine, coherent with the needs of poorly water soluble drugs.
ABSTRACT
Efavirenz, a widely prescribed anti retroviral drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating efavirenz –βCD– PVP K30/SLS inclusion complexes into tablets and to evaluate the effects of βCD, PVP K30and SLS on the dissolution rate and dissolution efficiency of efavirenz tablets in a 23 factorial study. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug – βCD – PVP K30/ SLS inclusion complexes. Drug – βCD- PVP K30/ SLS inclusion complexes were prepared by kneading method. Tablets each containing 50 mg of efavirenz were prepared by wet granulation and direct compression methods employing various βCD complexes as per 23 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz tablets formulated employing dug – βCD – PVP K30/ SLS inclusion complexes and prepared by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Efavirenz dissolution was rapid and higher from the tablets formulated employing drug- βCD- PVP K30 /or SLS inclusion complexes when compared to the tablets containing efavirenz alone in both wet granulation and direct compression methods. The individual as well as combined effects of the three factors involved i.e., βCD ( factor A), PVP K30( factor B) and SLS( factor C) were highly significant (P< 0.01) in enhancing the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz in both wet granulation and direct compression methods. Among the three factors βCD (factor A) gave highest enhancement in the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz tablets in both wet granulation and direct compression methods. SLS (factor C) alone gave low dissolution rate in both wet granulation and direct compression methods .Overall direct compression method gave higher dissolution rates (K1) and dissolution efficiency (DE 30) values than the wet granulation method in all the cases. Combination of βCD with either PVP K30 or SLS or both gave a significantly higher dissolution rate (K1) of efavirenz in both wet granulation and direct compression methods. Hence a combination of βCD with either PVP K30 or SLS or both is recommended to enhance the dissolution rate and efficiency of efavirenz tablets.
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The objective of the study is to evaluate the individual main effects and combined (or interaction) effects of Hydroxy propyl β cyclodextrin (HPβCD), poly vinyl pyrrolidone (PVP K30) and sodium lauryl sulphate (SLS) on the solubility and dissolution rate of efavirenz in a series of 23 factorial experiments. The solubility of efavirenz in eight selected fluids containing HPβCD, PVP K30 and SLS as per 23 factorial study was determined. The solubility of efavirenz was markedly enhanced by HPβCD (2.95 fold), PVP K30 (2.49 fold) and SLS (226.96 fold) individually. Combination of HPβCD with PVP K30 and SLS gave a markedly higher enhancement in the solubility of efavirenz than is possible with them individually. HPβCD in combination with PVP K30 and SLS gave respectively 4.05 and 387.63 fold increase in the solubility of efavirenz. Solid inclusion complexes of efavirenz - HPβCD were prepared with and without PVP K30 and SLS as per 23- factorial design by kneading method and were evaluated. ANOVA indicated that the individual main effects of HPβCD, PVP K30 and SLS and their combined effects in enhancing the solubility and dissolution rate (K1 )and dissolution efficiency (DE30 ) were highly significant (P < 0.01).HPβCD alone gave a 16.74 fold increase in the dissolution rate of efavirenz. HPβCD in combination with PVP K30 and SLS gave respectively 19.98 and 25.13 fold increase in the dissolution rate of efavirenz. HPβCD in combination with both PVP K30 and SLS gave highest enhancement (41.61 fold) in the dissolution rate of efavirenz. Combination of HPβCD with PVP K30 and SLS has markedly enhanced the solubility as well as dissolution rate of efavirenz than is possible with them individually. Hence a combination of HPβCD with PVP K30 and / or SLS is recommended to enhance the solubility and dissolution rate of efavirenz, a BCS class II drug.
ABSTRACT
Etoricoxib, a widely prescribed anti-inflammatory drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating etoricoxib – CD (βCD/ HPβCD) – Poloxamer 407 and etoricoxib – CD (βCD/ HPβCD) –PVP K30 inclusion complexes into tablets and to evaluate the effects of CDs, Poloxamer 407 and PVP K30 on the dissolution rate of etoricoxib tablets. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug – CD –Poloxamer 407 / PVP K30 inclusion complexes. Drug – CD- Poloxamer 407 / PVP K30 inclusion complexes were prepared by kneading method. Tablets each containing 60 mg of etoricoxib were prepared by wet granulation and direct compression methods employing various CD complexes and the tablets were evaluated for dissolution rate and other physical properties. toricoxib tablets made by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Tablets formulated employing βCD complexes disintegrated relatively more rapidly than those formulated employing HPβCD complexes. Etoricoxib dissolution was rapid and higher from the tablets formulated employing drug- CD- Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing etoricoxib alone and drug – CD complexes in both wet granulation and direct compression methods. In both the methods tablets formulated employing βCD complexes gave higher dissolution rates (K1) and DE30 values when compared to those formulated employing HPβCD complexes. Tablets formulated employing dug – βCD – Poloxamer 407 and drug – βCD – PVP K30 complexes and prepared by direct compression method gave higher dissolution rates, 0.0539 and 0.0459 min-1 respectively when compared to plain tablets (0.0124 min-1 ) as well as tablets containing drug – βCD complexes (0.0417 min-1). Hence a combination of βCD with Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate of etoricoxib tablets.
ABSTRACT
The present study was aimed to increase the solubility of the poorly water soluble drug (Gliclazide) by using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Gliclazide in solid dispersions when compared to pure drug. FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion.
ABSTRACT
Objective To prepare Wurenchun solid dispersion of alcohol extracts of Fructus Schisandrae Chinensis so as to improve the dissolution of its active compound in vitro.Methods The Wurenchun solid dispersions were prepared with various carriers and drug/carrier ratios by mixing the carrier in alcohol extractive solution of FSC directly,and the apparent solubility and dissolution of deoxyschisandrin in them were tested and compared.Results The apparent solubility and dissolution of deoxyschisandrin of Wurenchun solid dispersion(extracts: polyvinylpyrrolidone(PVP) K30=1∶3) were increased remarkably to 5.06 ?g/mL and 43.2% in water individually,including dispersed and dissolved drug whose particle size is below 0.22 ?m,compared with that of the self-prepared Wurenchun capsules.Conclusion Wurenchun solid dispersion made of PVP K30 can remarkably enhance apparent solubility and dissolution of the active compound in vitro.