Release profile of lidocaine HCl from topical liposomal gel formulation

Liposomal hydrogel formulations of lidocaine HCl, suitable for topical application, have been prepared and drug release properties in vitro have been evaluated. Liposomes composed of Soya lechitin and cholesterol, with lidocaine HCl, entrapped in the inner water compartment, were prepared by simple hydration method. Topical liposomal gel formulations were prepared by incorporation of liposomes into a structured vehicle (hydrogels of Carbopol 940 in concentration of 1.5, 1.75 and 2%). High percentage of encapsulated drug in liposomes has been obtained (over 70%). Liposomal gel formulations provided prolonged drug release rate. The concentration of gelling agent in a range 1.5-2.0% affected the release rate slightly. In vitro release data showed that release kinetic can be described as diffusion-controlled, while liposomes act as reservoir systems for continuous delivery of drug. Proposed formulations provided stable percentage of entrapped drug and drug release within an examination period of 3 weeks.     

Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia

In the present work attempts have been made to prepare the nanostructured lipid carrier (NLC) gel, by using minoxidil, which is preferably used in case of Alopecia, i.e. baldness pattern as a effective drug. The nine different formulations of Minoxidil-NLC (NLC1–NLC9) were prepared using solid and liquid lipids with Cholesterol and Soya lecithin in different concentrations by the melt dispersion ultrasonication method. Properties of NLC1–NLC9 such as the particle size and its distribution, the scanning electron microscopy (SEM), the drug entrapment efficiency (EE), and the drug release behavior were investigated. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadability, rheology, and in vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies. The formulated NLC3 was spherical in shape, with average particle size of 280 nm, zeta potential of ?42.40 mV and entrapment efficiency of 86.09%. Differential Scanning Calorimeter (DSC) measurements revealed that imperfect crystallization occurred in the inner core of the NLC particles. The drug release behavior from the NLC displayed a biphasic drug release pattern with burst release at the initial stage followed by sustained release. These results indicated that the NLC3 is a suitable carrier of minoxidil with improved drug loading capacity and controlled drug release properties. It has been observed that NLC gel produces the gel with good consistency, homogeneity, spreadability and rheological behavior. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 16 h. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nanoparticulate form helped us to attain the objective of faster onset yet prolonged action as evident from in vitro release.     

Validation of a quantitative determination method of diclofenac for in vitro bioequivalence evaluation of transdermal gel preparations

A quantitative determination method of diclofenac for studying the bioequivalence of transdermal gel preparations of this drug has been validated. It was established that the proposed method is precise, reproducible, and linear in a certain concentration range. The release of diclofenac from transdermal gels with different viscosities and from the reference preparation was studied using the paddle-over-disk technique. Drug release from the transdermal gel preparation was modeled using various mathematical laws including the Higuchi law, first-order kinetics, cube root, and Weibull function. An analysis of the experimental data showed that the release of diclofenac from gels proceeds by diffusion and obeys the Higuchi law. It was found that the rate of drug release from the gel depends significantly on the viscosity. Similarity coefficients were calculated in order to compare diclofenac dissolution profiles and to determine their equivalence. It was concluded that experimental samples of diclofenac gel with medium and high viscosity were equivalent to the reference preparation.     

SDS-aided immobilization and controlled release of camptothecin from agarose hydrogel.

Camptothecin (CPT), known to be an effective anticancer drug, has a limited therapeutic utility because of its poor water solubility. In this work, an approach has been made to overcome the limitation. CPT was first incorporated into the micelles formed from an ionic surfactant, sodium dodecyl sulfate (SDS) and the micellar drug aqueous solution was then used in preparation of the agarose hydrogel. It has been found that the presence of SDS greatly increased the solubility of CPT in water. For example, in 1 ml of 1.0 wt.% SDS water solution, 0.11 mg CPT could be solubilized (0.318 mM), which was 83 times the solubility in pure water. It was the hydrophobic cores of the SDS micelles that were able to accept the lipophilic drug to form stable drug-immobilized micelles. The formulation of a hydrogel using the drug-immobilized micelles has allowed us to obtain a unique and novel drug release system where the drug molecules are encapsulated by the micelles and the drug-containing micelles are dispersed in the gel network. The release of CPT from the so deliberately fabricated agarose hydrogel system has been studied as a function of surfactant concentration at 37 degrees C. The diffusion coefficients of CPT obtained by fitting to Fick's law ranged from 2.12 to 7.36 x 10(-7)cm(2)s(-1). The results showed that SDS prolonged the drug release by reducing the diffusion coefficient of CPT in the gel.     

乳酸环丙沙星温度敏感眼用凝胶的体外释放研究

目的研究乳酸环丙沙星温度敏感眼用凝胶的体外释放规律。方法采用无膜溶出模型考察凝胶溶出规律,采用紫外分光光度法进行药物含量测定。结果乳酸环丙沙星温度敏感眼用凝胶溶蚀和药物释放为零级动力学过程,凝胶溶蚀和药物释放呈良好的线性相关。结论凝胶溶蚀是决定药物释放的主要因素。     

The production and properties of gel precipitated aluminium hydroxide spheres containing imipramine

The production of aluminium hydroxide spheres containing imipramine by gel precipitation of liquid feed solutions has been described. Washing and heating procedures applied to the precipitated spheres markedly affected the rate of drug release from the spheres into 0·1m hydrochloric acid. Increasing the imipramine content of the spheres also altered the drug release rate. The effects described have been explained with reference to model theories of the precipitation and ageing of aluminium hydroxide gels in the presence and absence of ‘foreign’ anions.     

马来酸噻吗洛尔眼用温敏凝胶的处方筛选与体外释放评价

目的:筛选马来酸噻吗洛尔眼用温敏型凝胶优化处方,并对其体外释放进行评价。方法:选用泊洛沙姆P407、P188为载体材料制备眼用温敏凝胶,测定不同处方的凝胶前体溶液分别在未经处理和经人工泪液稀释条件下,从溶液态转变为凝胶态的胶凝温度,通过星点设计-效应面法筛选优化处方,并考察胶凝时间和释放行为。结果:根据温敏凝胶保存和使用的温度要求,筛选出优化处方为P407:P188(24.25%:1.56%)。前体溶液能够在34℃人工泪液中迅速形成凝胶,并在体外缓慢释放6 h以上。结论:经过筛选并制备出的噻吗洛尔温敏型凝胶具有良好的载药能力、稳定性及释放性能,满足眼用制剂质量要求和实际应用要求。     

In vitro release of lidocaine from pluronic F-127 gels

The release of lidocaine from aqueous, crystal clear and colorless gels of Pluronic F-127 (a polyoxyethylene-polyoxypropylene surface-active block polymer) has been studied in an in vitro release model which did not utilize a membrane. Pluronic F-127 forms micelles in aqueous systems and the gels are believed to be viscous isotropic liquid crystals. Due to their reverse thermal gelation behavior, good solubilization capacity, optical properties and low toxicity, they appear to have potential application as topical drug delivery systems. It has been found that the rate of lidocaine release was inversely proportional to its concentration, the concentration of Pluronic F-127 and electrolyte concentration (sodium chloride). Release of lidocaine was maximal at pH values close to its pK_a; however, release of the more water-soluble benzocaine (included for comparison purposes) was relatively pH-independent over the pH range studied. Since the apparent diffusion coefficient of lidocaine increased with increasing temperature, in spite of increasing macro-viscosity of the gel, it is apparent that drug is released by diffusion through the extramicellar aqueous channels of the gel matrix. Hence, the rate of drug release was determined by the micro-viscosity of the extramicellar fluid, the dimensions of the aqueous channels, and the equilibrium relationship of drug between the micelles and the external aqueous phase.     

Pulsatile drug release control using hydrogels.

Current research in the field of drug delivery devices, by which pulsed and/or pulsatile release is achieved, has been intensified. In this article several types of drug delivery systems using hydrogels are discussed that showed pulsed and/or pulsatile drug delivery characteristics. As is frequently found in the living body, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific site and time. Thus it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems, while minimizing undesired side effects. Special attention has been given to the thermally responsive poly(N-isopropylacrylamide) and its derivative hydrogels. Thermal stimuli-regulated pulsed drug release is established through the design of drug delivery devices, hydrogels, and micelles. Development of modified alginate gel beads with pulsed drug delivery characteristic is also described in this article.     

Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads.

Pectin has been investigated for its ability to produce solid calcium pectinate gel (CPG) beads containing bovine serum albumin (BSA). Several factors can influence the properties and release characteristics of the CPG beads. In this study, the effect of calcium concentration, hardening agent and drying condition on the encapsulation and release characteristics of BSA from the matrix gel beads made of calcium pectinate were studied. BSA release studies under conditions mimicking mouth to colon transit have shown that calcium pectinate protects the drug from being released completely in the physiological environment of the upper gastrointestinal tract, and is susceptible to the enzymatic action with consequent drug release. In addition, the release of BSA from CPG beads was strongly affected by calcium concentration and drying condition. However, the release was not particularly affected by the presence of hardening agent at the concentration of 1% or lower. Since the release of BSA as a model protein drug could be controlled by the regulation of the preparation conditions of CPG beads, the CPG beads may be used for a potential oral controlled release system for protein drugs.     

Emerging pressure-release materials for drug delivery

Drug delivery systems for non-specialist uses and application under field conditions are required for medical action in disaster situations and in developing countries. A possible solution for drug delivery under those conditions might be provided by mechanical manipulation of host–guest interactions that could allow drug release control by simple human actions such as hand motion. This editorial article presents recent research developments on control of molecular recognition, capture and release involving macroscopic mechanical motions. In particular, pressure-induced drug release from a cyclodextrin-linked gel has been used to realize controlled release of entrapped drugs upon applying an easy-to-perform mechanical procedure. These easy-action-based drug delivery systems can be applied at will by unskilled staff or patients and are expected to be used to assist medically patients in less-favorable environments anywhere in the world.     

难溶性药物凝胶制剂研究进展

凝胶制剂作为透皮给药系统（transdermal drug delivery system，TDDS）的一种新型制剂，经皮肤给药发挥全身或局部治疗作用，有使用方便、安全性好、释药平缓持久等优势，成为近年来药物制剂研发的重点之一。但现有的大多数化合物均为难溶性药物，在凝胶制剂方面的应用受限。近年来，许多新型药物载体包括纳米化技术、包合物、固体分散体等被广泛用于难溶药物增溶以及增强药物皮肤透过能力。文章详细综述了各种药物载体的特点及其在凝胶制剂的应用优势和缺陷，并汇总了现FDA难溶性药物凝胶产品的上市情况以及各种增溶技术在凝胶制剂的具体应用，为凝胶制剂未来的研发方向提供理论基础及实践案例。     

酮洛芬果胶钙凝胶小球和海藻酸钙凝胶小球的制备及性能比较

目的酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球的制备及性能比较。方法利用果胶、海藻酸钠及二者不同比例,以酮洛芬为模型药物采用滴制法制备凝胶小球,考察2种多糖物质对药物包封率和释放行为的影响。利用大鼠肠囊外翻实验对凝胶小球的生物黏附性能进行比较,通过对释放机理的探讨和凝胶小球溶胀性的测定进一步证明2种凝胶小球释药行为的不同。结果酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球均具有良好的生物黏附性能,果胶钙凝胶小球主要通过溶胀作用缓慢释药,而海藻酸钙凝胶小球的释药与凝胶小球慢慢吸水后骨架溶蚀有关。结论酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球通过与生物黏膜的紧密结合缓慢释药,而二者的释放行为有所不同。     

Formulation of an antispasmodic drug as a topical local anesthetic

Mebeverine hydrochloride, a spasmolytic agent on GIT smooth muscles, was reported to have a local anesthetic effect. Thus, it was desired in this study to formulate mebeverine HCl into a gel that could be used locally in the treatment of different oral painful conditions. Poloxamer 407 (P-407) was used as the base for this gel. Different additives were used to enhance drug release from the preparation while others were used to enhance the residence time for the preparation. Different formulae were characterized in terms of drug release and mucoadhesion. The formula which has shown the best compromise between the aforementioned parameters was selected for clinical evaluation in comparison to Lidocaine HCl gel and rheologically examined. The best drug release enhancer was cetrimide (0.005%, w/w), while hydroxypropylcellulose (0.5%, w/w) as a mucoadhesive additive has shown the best compromise between fast drug release and mucoadhesion. The gel formula (G) has shown a better pain reduction efficiency (p=0.0078) and longer duration (p=0.0313) than Lidocaine HCl gel. Histopathological examination has shown no change in the inflammatory cells count of rat oral mucosa. Therefore, it could be concluded that (G) is very promising as a local anesthetic preparation for the treatment of different oral painful conditions.     

Formulation and evaluation of new long acting metoprolol tartrate ophthalmic gels

The rationale of the present work is to formulate and evaluate metoprolol tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new ocular gel delivery system; this is our way and method to increase its contact to the cornea, giving a longer time of drug contact to the eye and slow possible release from the preparation. Metoprolol tartrate is chosen as a candidate for gel formulation because although it has been available for a few years as ophthalmic solutions, it has not been marketed as an ocular gel yet. Two polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different concentrations in this study. Metoprolol tartrate was used in two concentrations, 0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH measurement, in vitro release, rheological study and differential scanning calorimetry (DSC). Results showed that all formulations were clear, showed pH within the acceptable range suitable to be administered in the eye, and exhibited pseudoplastic flow behavior. DSC results concluded that, MT was compatible with different polymers used. In vitro release results showed that the release rate of metoprolol tartrate from gel preparations decreased as an inverse function of polymer concentration, and the release rate of the drug increased as the initial concentration increased. Intra-ocular pressure (IOP) measurements of rabbit’s eye treated with 1% (w/w) metoprolol tartrate in gel formulations with different concentrations of the polymer were determined. Carbopol 934 gel formulations showed that this polymer extended the duration of pressure reducing effect of MT to more than 5hr when compared with Pluronic F127 gel formulations. The area above the curve (AAC), maximum response, time of maximum response (t_max), and the duration of the drug action were also calculated.     

Carrageenan gels for oral sustained delivery of acetaminophen to dysphagic patients

We have designed gel formulations for the oral administration of acetaminophen with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the stomach to achieve a sustained release of this drug. Gels formed by agar and ι-carrageenan were assessed for suitable gel strength and in vitro and in vivo release characteristics. Comparison of 1.5% ι-carrageenan gel with 0.5% agar gel demonstrated improved sustained release properties of the ι-carrageenan gel. Gel formed by ι-carrageenan has suitable rheological and sustained release characteristics for potential use as vehicles for oral delivery of drugs to dysphagic patients.     

Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation

The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.     

Some factors affecting the release of imipramine from gel-precipitated aluminium hydroxide spheres

Changing the pH of the dissolution medium has been found to affect the release of imipramine from gel-precipitated aluminium hydroxide spheres. Release from unwashed, unheated spheres into solutions of pH 1.2 was controlled by dissolution of the gel matrix, whereas that into solutions of pH 3 and pH 5 appeared to be under diffusion control. The liberation of drug from unwashed, heated spheres into the media of higher pH exhibited more complex kinetics. Washed spheres failed to release significant amounts of imipramine into the solutions of pH 3 and 5. Changing the ionic strength of the media had little effect on drug release. These phenomena have been explained with reference to model theories of the precipitation and ageing of aluminum hydroxide gels and their pH-solubility profiles.     

Sustained release of lidocaine from Poloxamer 407 gels

In this work, we show that alteration of P407 gel content can affect drug release rates. The inorganic salts and PEG 400 commonly included in the formulation of P407 gels can also change the rate at which a drug is released. Lidocaine was selected as a model drug because, although widely used in the treatment of pain, its use is limited by short duration of its effects. The use of P407 gels prolongs the residence time of the lidocaine at the injection site, sustains drug release and increases therapeutic efficacy. Release studies were performed in a diffusion system. During release, data followed the Higuchi square root law time kinetic (r>0.98). Increased polymer concentration in the gel increases viscosity and reduces lidocaine release rates and diffusion coefficients via extended gel dissolution time and prolonged drug diffusion through the gel matrix. Lidocaine release rates and diffusion coefficients increased in gels composed of NaCl or PEG 400 aqueous solution. Because these additives are hydrophilic, they reduce gel dissolution time, thereby accelerating drug diffusion. Poloxamer is biocompatible and the results support the possibility of using Poloxamer gel as a sustained release injectable formulation.     

加替沙星pH敏感眼用原位凝胶体外释放的研究

目的研究加替沙星pH敏感眼用原位凝胶的体外释药特性与机制。方法采用改良桨法考察加替沙星pH敏感眼用原位凝胶的释药规律,并用无膜溶出法研究其释放机制。结果凝胶溶蚀和药物释放随着振荡频率和释放面积的增加而加快。其溶蚀度与释放度有明显相关性。结论体外的溶蚀行为与释放行为遵循零级动力学方程,凝胶溶蚀是决定药物释放的主要因素。