Effects of interacting variables on the release properties of chloroquine and aminophylline suppositories (original) (raw)

Effects of surfactant characteristics on drug availability from suppositories

Die Pharmazie, 2008

The addition of surfactants to suppository formulations is referred to in the scientific literature, but their effects on drug availability remain uncertain. Surfactants are reported to improve drug dispersion into hard fatty excipients, to increase the spreading of the melted suppository on the rectal mucosa leading to a greater contact surface, to reduce the viscosity of the molten mass and to reduce the pathway of drug particles to the interface. In the present study a systematic investigation based on tensiometric and rheological methods was carried out to evaluate the effects of nonionic surfactants with different HLBs (hydrophilic-lipophilic-balance) on drug availability and to clarify the possible mechanisms involved in the release process. The relationship between the melted suppositories and a membrane simulating the rectal barrier were investigated in the course of the in vitro release test by measuring their energy characteristics. At the same time, the potential influenc...

Effect of interacting variables on the mechanical and release properties of chloroquine phosphate suppositories

The individual and interaction effects of type or nature of suppository base (N), concentration of surfactant (C), and storage (S) on the mechanical and release properties of chloroquine phosphate suppositories have been studied using a 2 3 factorial experimental design. Suppositories (1g) containing 100mg chloroquine phosphate each with or without 2%w/v Tween 20 as adjuvant, were prepared in Suppocire® AS2 and Witepsol® H15 bases. The mechanical properties of the suppositories were determined using crushing strength and dissolution properties were assessed using dissolution times (t 50 and t 80 -time for 50% and 80% drug release), and rates. The concentration of surfactant had the highest individual effect on the release properties of the suppository formulations while storage had the lowest effects. Thus, the type of suppository base and concentration of surfactant used in suppository formulations need to be carefully chosen in order to obtain suppositories of desired mechanical and drug release properties.

Quantitative analysis of the effects of drug-base ratio on the physical and release properties of paracetamol suppositories

The Pharma Innovation Journal, 2017

Paracetamol is available in various strengths as rectal suppositories, hence the need to evaluate the effects of drug-base ratio as a formulation variable on the physical and release properties of paracetamol suppositories formulated with a lipophilic base. Suppositories, each containing 60 mg to 500 mg of paracetamol in cocoa butter were prepared by fusion method using 1 g and 2 g capacity moulds. Physical and dissolution properties of the suppositories were determined by established methods. Quantitative effects of the drug-base ratio on physical and release properties of the suppositories were analysed using 2 factorial experimental designs. The independent and interaction coefficients of the two variables deviated from zero, indicating significant effects on the physical and release properties of the suppositories. While First-order release kinetics was observed for all the formulations, there was a significant change in the release rate constants with variation in the drug-base...

The role of various surfactants on the release of salbutamol from suppositories

Il Farmaco, 2004

Salbutamol is a selective b 2 -adrenoreceptor agonist with different pharmacological effects. In this research because of the simplicity of suppository application in elderly and its higher plasma concentration than tablets as well as its particular indication in premature labour, salbutamol suppositories were prepared. The suppositories were formulated containing 10 mg of the drug and Witepsol H15, the oleaginous soluble base using melting method. To optimize the release rate of drug, different surfactants namely, sodium lauryl sulphate (SLS) as an ionic surfactant and Tween 80 as well as Arlacel 60 as non-ionic surfactants with different HLBs were chosen. The effect of surfactant concentration on the release rate of salbutamol from suppositories were also investigated. All prepared formulations fulfilled the specifications set down in British Pharmacopoeia. The results showed that Tween 80 (2%w/w) and SLS (0.75%w/w) caused an increase in dissolution rate of salbutamol from suppositories. As anionic surfactants, such as SLS, cause greater damage on mucosa than non-ionic surfactant, such as Tween 80, this study recommended that Tween 80 could be added in suppository formulation in order to increase the dissolution rate of salbutamol. It was also shown that the release rate of salbutamol altered linearly with the amount of Tween 80 in suppository formulations.

Surfactants solubility, concentration and the other formulations effects on the drug release rate from a controlled-release matrix

2014

Surfactant effects on the drug release from controlled release systems have been widely studied. These effects are dependent on the surfactant physical properties such as structure, charge, solubility and concentration. In addition, presence of excipients in the matrices can modify the surfactants effects. Here we investigated the effects of surfactant solubility and concentration of excipients on the drug release. Two cationic surfactants (cetrimide and cetylpyridinium chloride), two anionic surfactants (sodium lauryl sulfate and sodium taurcholate) and the amphoteric surfactant betaine were used. The used dissolution medium was simulated gastric fluid pH 1.2. The results revealed that surfactants of the same charge with the drug showed increase of drug release rate in concentration below the surfactant critical micelle concentration (CMC), while the increase in the drug release was to a less extent in surfactant concentration above its CMC. On the other hand, drug release rate was increased with surfactant solubility and vice versa. Surfactants of different charges with that of the drug resulted in a decrease in the drug release rate, depending on surfactant solubility and the excipients. The amphoteric surfactant increased the drug release rate depending on surfactant solubility and concentrations.

Study of Dissolution Kinetics for Poorly Water-Soluble Drugs from Ternary Interactive Mixtures in Comparison with Commercially Available Capsules

Objective The main objective of this work was to study the dissolution kinetics of poorly water-soluble drugs, indomethacin and ibuprofen, from formulated capsules or interactive mixtures containing fine lactose (FL), as ternary additive, and coarse lactose as carrier compared with selected commercially indomethacin capsules and to investigate the role of FL-drug size ratio on the dissolution. Results and Discussion It was found that the addition of FL in lactose-indomethacin capsules enhanced the dissolution of indomethacin while it has decreased the dissolution of ibuprofen from the lactose-ibuprofen mixtures. The particle size distributions for drugs and fine lactose used in this study suggested that the difference in dissolution behaviour for the two drugs could be due to the FL-drug ratio. Results obtained from the application of different dissolution kinetic equations showed that the first-order equation can best describe the kinetic of the dissolution for Rothacin®, Indylon®, Indomin® and ternary-formulated capsules of indomethacin, while the dissolution from the binary-formulated indomethacin capsules showed that the dissolution cannot be described by zero-order or first-order equations. For ibuprofen mixtures, the results showed that the release followed the firstorder kinetic for both systems, binary and ternary mixtures. Results obtained from Peppas equation showed that all indomethacin formulations used in this study released the drug by Fickian release with release exponent (n) <0.45, while all ibuprofen formulations used in this study released the drug by non-Fickian (anomalous) release with release exponent (n) >0.45 and >0.89.

Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method

Journal of Controlled Release, 1998

Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of solid oral dosage forms. The objective of the present study was to investigate the effect of delivery system positioning in accordance with the USP 23-recommended dissolution methods and the proposed modification on drug release from controlled release systems having different operating release mechanisms, namely, swellable floatable, swellable sticking and osmotic pump. The delivery systems were evaluated by placing each dosage form either in the dissolution vessel in accordance with the USP 23 methods or over / below a designed ring / mesh device for achieving full surface exposure to the dissolution medium for sticking or floatable systems respectively. Results indicate that the overall release profiles from the sticking and floatable systems of theophylline are sensitive to their positioning in the dissolution vessel (P,0.05). Furthermore, release of diltiazem hydrochloride from the sticking system also demonstrated sensitivity (P,0.05). In contrast, the floatable dosage form of this latter drug with the application of a helical wire sinker, or when it was placed below the ring / mesh assembly, or by allowing the dosage form to float, did not show sensitivity (P.0.05) for the overall release behavior. This was attributed to the greater solubility of diltiazem hydrochloride (50% solubility in water at 258C) in comparison to theophylline which is a sparingly soluble drug (0.85% solubility in water at 258C). Drug release from the osmotic pump appeared to be identical under the given experimental conditions (P.0.05). Statistical analysis of data was performed by comparing the t , t , t ; mean dissolution times (MDT , MDT , 50% 70% 90% 50% 70% MDT); the ''difference factor, f '' and ''similarity factor, f ''. It is concluded that the results derived from the application 90% 1 2 of the ''similarity factor, f '' are superior to the individual time points (e.g. t %) and MDT % values in differentiating 2 x x between overall release patterns or the border line release profile differences. It also became apparent that in the case of the swellable sticking systems full surface exposure to the dissolution medium results in greater release rate. For the osmotic pump the required osmotic pressure threshold necessary for constant rate drug delivery appears to have reached independent of the hydrodynamic conditions. A successful and more accurate evaluation of dissolution data can be derived when full surface exposure is considered and this can be accomplished by dissolution method modification with the aid of the designed ring / mesh assembly.

Synergistic Effects of Disintegrants on Release of poorly Water soluble drug

International Journal of Pharmaceutical and Life Sciences, 2012

We have done research work in lab to find out proper formulation of immediate release tablet by using of various types of disintegrants (crospovidone, sodium starch glycolate and sodium carboxymethylcellulose), in order to examine the effect of mode of absorption of disintegrants on release mechanism from tablets. Acetaminophen, a poor soluble drug was used as a model drug to estimate its release pattern from different formulations. The USP paddle method was selected to perform the dissolution profiles carried out by USP apparatus 2 (paddle) at 50 rpm in 900 ml phosphate buffer pH 5.8. Successive dissolution time, time required for 25%, 50% and 80% of the drug release (T 25 %, T 50 %, T 80 %) was used to evaluate the dissolution results. A One way analysis of variance (ANOVA) was used to recognize the result. Statistically significant differences were found among the drug release profile from all the formulations except mode of addition of crosspovidone. At a fixed amount of disintegrants, extragranular mode of addition seemed to be the best mode of incorporation. The best release was achieved with the sodium carboxymethylcellulose and sodium starch glycolate containing formulations. The T 50 and T 80 values were analytical of the fact that the drug release was faster from tablet formulations containing carboxymethylcellulose and sodium starch glycolate. The drug release was very much negligible difference by the mode of crospovidone addition. Two formulations found very small T 50 and T 80 values indicating very much faster release. From the all formulations corresponded extragranular mode of addition could be the best mode of incorporation. The drug release was unaffected by the mode of crospovidone addition. The mode of incorporation of disintegrants suggested enchancing the release of poor soluble drugs.

Studying the factors that impact the dissolution characteristic of complex drug product

Pharmaceutical Development and Technology, 2019

This article summarizes the critical factors involved in product development of a single dosage form formulated by compacting ethyl cellulose (EC) coated controlled release pellets into a tablet. The greatest challenge associated with this type of complex system is to minimize the effect of compression on the drug release. The effects of compression on the drug release were optimized with combination of the following factors (1) particle size of the core pellets, (2) the selection of the coating polymer's viscosity grade, and (3) emergence of cushioning agents. The optimization of these factors provided superior protection for the controlled release coated pellets; therefore, the desired drug release from the tablet was successfully achieved as designed. However, the drug release rates from the coated pellets before and after the compression were minimized and exhibited only a slight difference.