For healthcare professionals. Compounded preparations are dispensed on a doctor’s prescription.
Short answer: Liposomal encapsulation of a misai kucing (Orthosiphon stamineus) ethanolic extract has been tested in laboratory and rat studies. In vitro, soybean-phospholipid liposomes raised the extract’s solubility from 956 to 3,979 µg/ml (PMID 24674107). These findings describe formulation behaviour in the laboratory and in animals, and they do not establish any effect in people.
The formulation problem
A formulation study of Orthosiphon stamineus describes the herb’s medicinal value as limited by a practical problem: “poor solubility of the active principles limits its medicinal value” (BMC Biotechnology, 2014; PMID 24674107). A later oral toxicity study describes the same issue on the oral route, stating that its lipophilic compounds “suffer from poor aqueous solubility which limits the OS oral bioavailability and therapeutic applications” (BMC Complementary and Alternative Medicine, 2015; PMID 26467526).
These are statements about the extract’s physical chemistry, not evidence of any effect in people. The formulation question for a prescriber is therefore narrower: does a liposomal liquid change how the extract dissolves, releases and passes a membrane? That is a laboratory question, and the answer is set out below.
What the formulation research did and found
In vitro and ex vivo work (PMID 24674107)
Soybean-phospholipid nano-liposomes were prepared from an ethanolic extract by the conventional film method, then characterised for solubility, entrapment, particle size, release and absorption. The abstract reports that solubility rose from 956 ± 34 to 3,979 ± 139 µg/ml, with an entrapment efficiency of 66.2 ± 0.9% (PMID 24674107). In a release study, the abstract reports 94 ± 0.1% release from the non-formulated extract and 62.4 ± 0.1% from the liposomes (PMID 24674107).
The abstract also reports “reversible agglomeration at pH 1.6” (PMID 24674107). Absorption was measured in everted rat intestinal sacs, an ex vivo model, and the abstract reports “substantial improvement in permeability” for several named flavones (PMID 24674107). These results are in vitro or ex vivo. They are not human absorption data.
Rat toxicity and in vitro genotoxicity (PMID 26467526)
A 28-day oral study in Sprague Dawley rats gave the nano-liposomal ethanolic extract at 250, 500 and 1,000 mg/kg/day. The abstract reports no significant difference from control in food and water consumption, body weight change, haematological and biochemical parameters, relative organ weights, gross findings or histopathology (2015; PMID 26467526). In vitro, the abstract reports that the extract “did not have any potential to induce gene mutations” in S. Typhimurium (PMID 26467526). The acute study reports an LD50 greater than 5,000 mg/kg in rats (PMID 26467526).
These are animal and laboratory safety findings. They do not establish safety in people, and they are not a dosing guide.
Study table
| Design | Model | Delivery system | Finding as reported | PMID |
|---|---|---|---|---|
| Formulation, solubility, release and permeability study | In vitro, and ex vivo everted rat intestinal sacs | Soybean-phospholipid nano-liposomes of ethanolic extract | Solubility 956 to 3,979 µg/ml; entrapment 66.2%; release 94% (extract) and 62.4% (liposomes); agglomeration at pH 1.6 | 24674107 |
| 28-day oral toxicity study and in vitro genotoxicity test | Rats (oral, 250 to 1,000 mg/kg/day); in vitro bacterial gene-mutation test in S. Typhimurium | Nano-liposomes of ethanolic extract | No significant difference from control in measured parameters; no potential to induce gene mutations in the strains tested | 26467526 |
How to read the solubility and safety figures
Each figure above comes from a different model, and the models do not add together. The solubility and entrapment numbers come from a laboratory preparation of the extract in liposomes, measured in vitro (PMID 24674107). The release figures compare the non-formulated extract with the liposomes (PMID 24674107). The permeability result comes from everted rat intestinal sacs, an ex vivo model, and applies only to the flavones the abstract names (PMID 24674107). The rat toxicity figures come from a separate study of a nano-liposomal preparation given by mouth for 28 days, and the genotoxicity result is a bacterial test (PMID 26467526). A prescriber should not carry a solubility figure from one model into a statement about absorption in a patient.
What is still unknown
The formulation records above are in vitro, ex vivo or animal studies. They describe no human pharmacokinetic study, no human dose-finding study and no clinical outcome. Whether a liposomal liquid delivers more of the extract’s flavones into a patient’s circulation is not established by these records. The extract standard, the flavone content per dose and the stability of a finished liquid over its beyond-use period are also not established here.
How this approach could be prepared at Lynnity
A liposomal oral liquid is one of the non-sterile forms Lynnity prepares. Liquids, suspensions and other forms are each prepared in a liposomal or an ordinary form, to a prescriber’s specification for one named patient (see the liposomal compounding overview). For this extract, the prescription specifies the extract, its strength per dose, the liposomal vehicle and the directions. The preparation is made under Good Compounding Practice (GCP). This describes what a prescription may request. It is not a statement that a particular preparation has been made or tested.
Where the evidence stops
Both formulation records examine a laboratory preparation of one ethanolic extract. The liposomal results are not transferable to other extracts, other lipid systems or other flavone profiles. The toxicity study tested one preparation in rats for 28 days, and it does not describe a longer course. A prescriber weighing this option should treat the findings as formulation evidence, and should set the clinical question separately.
How to prescribe
A liposomal misai kucing liquid is prepared only on a registered doctor’s prescription, for one named patient, under Good Compounding Practice (GCP). The prescription must state:
- the active, Orthosiphon stamineus (misai kucing) ethanolic extract, with the extract standard the prescriber specifies;
- the strength per dose;
- the vehicle, a liposomal preparation, and the form, an oral liquid;
- the quantity and the directions for use, with the review date.
Send the signed prescription through the contact page at https://www.lynnitypharma.com/contact-us/.
Related reading: the liposomal formulation brief template for KL prescribers and the liposomal compounding pharmacy guide. Laboratory standards are described on the GCP laboratory page.
Reviewed by Vitthia Rama Murti, RPh (RPh 15632).
Frequently asked questions
Does liposomal encapsulation improve the solubility of misai kucing extract?
In laboratory work, yes. Soybean-phospholipid liposomes raised the solubility of an ethanolic extract from 956 to 3,979 µg/ml, with an entrapment efficiency of 66.2% (PMID 24674107). These are in vitro results. They do not show how much of the extract reaches the bloodstream of a person.
Is there human clinical evidence for a liposomal misai kucing liquid?
The formulation studies described here are in vitro, ex vivo or in rats. They do not include a human study of a liposomal misai kucing liquid, and they do not establish any effect in people. A prescriber weighing this formulation should treat these records as formulation evidence only.
How was the toxicity of the liposomal extract tested?
In a 28-day oral study in rats, doses of 250, 500 and 1,000 mg/kg/day produced no significant difference from control in the parameters measured (PMID 26467526). In a bacterial gene-mutation test in S. Typhimurium, the extract did not have any potential to induce gene mutations (PMID 26467526). These are animal and laboratory findings, not a dosing guide for people.
What must a prescription for a liposomal misai kucing liquid state?
The prescription must state the extract and its standard, the strength per dose, the liposomal vehicle, the form (an oral liquid), the quantity and the directions for one named patient. The preparation is made on a registered doctor’s prescription under Good Compounding Practice (GCP).