Principles, Applications and Limitations of the Liquisolid System of Drug Delivery: A Review
Abstract
The liquisolid system of drug delivery continues to find usefulness as a potent means to circumvent solubility and dissolution challenges commonly encountered during drug formulation and medicine development in the pharmaceutical industry. Originally invented by Spireas, the technique has gained acceptance and improved over the years, in the types of excipients used, nature and class of drug formulated and its applications not only in transforming lipophilic and poorly soluble drugs to solid dosage forms with enhanced bioavailability, but also now gaining popularity in modified delivery, photoprotection and minimizing the effect of pH on drug release. This review thus highlights the foundational principles of the liquisolid technique, examines current methods employed and modern applications of this technique. It also gives present knowledge of this delivery technique and its limitations. A systematic approach to the search of published literature in standard databases (Pubmed, Google Scholar, Researchgate) was carried out using specific search terms and operators that provided available works as information sources for this review. Critical evaluation of obtained literature from the database was adopted to extract data on the principles and current applications of the liquisolid systems beyond its intended initial use. The prevailing mechanism for enhancing bioavailability via the technique is improved wetting and drug presentation in well dispersed or soluble state; minimal pH influence is based on the phenomenon of saturation solubility of the drug in the nonvolatile vehicle; and photoprotection is due to high refractive and diffraction capacities of the coating materials used. This work concludes by presenting the identified and potential limitations of the liquisolid technique. It gives expert opinions on how these are being circumvented and future perspectives on this ever-unfolding promising drug delivery strategy. It will be an invaluable contribution to current literature in drug development research employing liquisolid techniques for drug delivery.
Table 2: Merits and demerits of the liquisolid system
Introduction
The growing interest in the use of liquisolid systems in drug formulation and delivery studies has been related to its invaluable contribution to circumventing poor drug solubility, enhancing bioavailability and presenting several delivery strategies with desirable therapeutic outcomes1.
Solubility, dissolution and bioavailability rank highly as parameters considered during the development of potential therapeutic agents for use as medicines because sooner or later, all medicines must be in solution to be absorbed or reach desired drug concentration in systemic circulation for therapeutic efficacy2,3. However, the successful transformation of a potent drug into medicine is often beset by challenges of these physicochemical parameters or those related to them. Solubility and dissolution rate of a drug can thus significantly influence its absorption, determine its bioavailability in the circulatory system and expectedly influence the expected pharmacological response1,4.
Drugs with poor water solubility are generally formulated and used as high-dose medicines with high dosage regimens so that, after administration (for example via oral route), the fraction of it that goes into solution could reach therapeutic plasma concentrations5. Sadly, high-dose medicines could mean exceeding the safety limits of the drugs and approaching toxicity, escalated untoward effects and increased production costs. As medicinal chemists and formulation scientists continually search for and employ strategies to improve the rate and amount of poorly soluble drugs that go into solution, the liquisolid system of drug delivery is now gaining attention. Thus in this paper, this technique will be well explored in terms of its principles, its application and limitations associated with it. This work will also address how these limitations are being overcome. First, a background of poor drug solubility will be presented, how widespread the problem is and common strategies that have been employed to improve it will be highlighted.
Generally, when discussing solubility and dissolution studies of drugs, the solvent of interest is usually an aqueous medium or one that is water-miscible because it is the main component of human body fluids where administered drugs will dissolve and subsequently be absorbed. This also explains why it is also the widely used solvent for liquid pharmaceutical formulations. In medicine development and manufacture of new chemical entities and candidates, the unprecedented incidence of low aqueous solubility is a major problem. One possible reason is that most drugs developed as medicines are either weakly acidic or weakly basic, thus having poor aqueous solubility. Yet these drugs must be present in an aqueous solution at the site of absorption to be taken up by the body and utilized.
The recent unlimited leap in the sphere of drug discovery resulting from the interplay of combinatorial chemistry, high throughput screening and computer-aided-drug designs and modeling has made possible rapid drug synthesis, optimization and drug-receptor simulation studies in silico6. This progress has churned out a number of drug molecules that can effectively and selectively interact with receptors (or ligands) within the body to elicit biological activity. These resulting available drug molecules or candidates, however, are highly hydrophobic, show a slow dissolution rate and are poorly water soluble2,7. No doubt, an indication of the magnitude of solubility challenges in the development and manufacture of medicines.
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Table 3: Commonly used carriers for liquisolid delivery and their peculiar characteristics41
| Classes of carriers or coating material | Specific examples | Specific surface area (m 2/g) | Absorption capacity (mL/g) |
|---|---|---|---|
| Polysaccharides | Starches (tuber starches) | 0.6-4.35 | 0.96-1.5 |
| (corn starches) | 1.22-1.26 | ||
| Microcrystalline cellulose (Avicel PH 101) | 1 | 0.04-0.08 | |
| Amorphous cellulose | 12-22 | ||
| Lactose | 0.35 | ||
| Sugar alcohol | Sorbitol | 0.37-1.05 | |
| Phosphates | Fujicalin® (anhydrous dibasic calcium phosphate) | 27~40 | 1.2 |
| Dicalcium phosphate dihydrate (DCPD) Florite® | 0.3 | 1-1.3 | |
| Silicates | Neusilin (magnesium aluminometasilicates) Aerosil®200 | 300 | 3.4 |
| Microsilica | 200 | 1.7 | |
| 78 | 2.9 | ||
| Ordered mesoporous silicates | 1030-1500 | 7.8 |
Source: Principles, Applications and Limitations of the Liquisolid System of Drug Delivery: A Review, Daniel Ekpa Effiong, Godswill Chukwunweike Onunkwo, Review Article, Open Access, Volume 19, Issue 1, https://doi.org/10.3923/tmr.2024.178.198
Read also our introduction article on Sorbitol here:
