Après 2 Mois

Salt formation: an effective means to improve the physical and chemical properties of drug molecules and enhance the druggability of drugs

In drug development, drug forming research, including pharmacodynamics, pharmacokinetics, and early safety evaluation of drugs, is required to determine whether the active compound has the potential to be developed into a pill. The drug-forming properties of drugs are also an essential part of the drug-forming evaluation, and salt formation is one of the effective means to improve the physicochemical properties of drug molecules and enhance drug-forming properties.

Many drugs are salts of organic acids or bases. The salt formation can make some oily organic acids or organic bases solid, which is conducive to preparing concrete dosage forms. Moreover, the salt formation of drugs increases the water solubility, which is conducive to preparing some aqueous dosage forms, such as water injection and oral liquid. The salt formation process is often a purification process, which removes the impurities mixed in the drug that cannot become salt, etc. So what are the benefits of salt formation in drug development studies?

1,Salt formation of drugs can change the solubility of drugs and improve drug-forming properties

The solubility of drugs affects their pharmacokinetic properties, chemical stability, and the choice of dosage form, which is an essential element in evaluating drug-forming properties. A salt formation can change the solubility of drugs and improve the water solubility of drugs through salt formation, which is the primary method to develop intravenous injections of drugs, such as the poor water solubility of diuretic etanercept, which is mainly available in tablet form.

Still, its sodium salt has better water solubility and can be used to prepare intravenous injections. The free base of the antipsychotic haloperidol is also marketed mainly as a tablet due to its low solubility. At the same time, its lactate can be used to prepare injectable solutions with improved solubility.

Sometimes it is necessary to prepare extended-release dosage forms by reducing the solubility of the drug. In this case, it is required to form a salt of the drug with an acid or base of higher relative molecular mass and hydrophobicity. For example, the commercially available dosage forms of antidepressant trazodone hydrochloride are tablets, oral solutions, etc. The study of trazodone in salt found that its p-toluenesulfonate and dihydroxynaphthalate are much less soluble in water than sulfate, and hydrochloride p-toluenesulfonate is more suitable for the preparation of slow-release oral formulation.

2,Salt formation can improve drug stability

Formulation evaluation also needs to rely more on data generated from pre-prescription research work, such as extreme pH, high temperature, freeze-thaw, light, forced oxidation, and other forced degradation experiments to understand the stability of drugs. Medicilon offers a full suite of chemical drug development services integrated from start to finish. We provide a one-stop service through pre-prescription studies, drug analysis, drug stability studies, formulation development, and complete CMC services.

The stability of the drug is directly related to its dosage form and the selection of production and packaging conditions, and it even affects the effect of the final preparation. Some researchers chose the insoluble phenazopyridine (PAP) as a model drug and improved the solubility and stability of phenazopyridine through drug co-crystals and salts.

The marketed product of phenazopyridine is phenazopyridine hydrochloride. Still, the peak plasma concentration in rats is only 10-20 ng after 200 mg dose administration, and it is for these reasons that the clinical application of PAP is limited. Therefore, the investigators prepared one eutectic formed by phenazopyridine with phthalimide (1) and two salts with 4-hydroxyphenyl acetic acid (2) and saccharin (3) by solution method and spiked grinding method, respectively, and their structures obtained by X-ray single crystal diffraction showed the presence of hydrogen bonding between phenazopyridine and all three eutectic ligands, collectively called hydrogen bonding complexes [1].

X-ray powder diffraction, DSC, and IR characterized it. The powder solubility of the three hydrogen-bonded complexes was measured, and the hygroscopicity of the solid powders was examined at 85% and 98% relative humidity for 1, 3, 5, 7, 10, 14, 21, and 28 days. The experimental results showed that the melting points of the three hydrogen-bonded complexes were all between phenazopyridine and eutectic ligands; the powder solubility of 1-3 was 10, 7.5, and 2 times that of PAP, respectively; the hygroscopicity was much lower than that of PAP and its hydrochloride under the conditions of 85% and 98% relative humidity. According to the above results, it is clear that 1-3 has a good prospect for improving the bioavailability and stability of phenazopyridine.

3,Salt formation can change drug compliance

Drug formulation should be safe, effective, stable, and easy for patients to accept, i.e., good compliance. An essential indicator of compliance with oral formulations is the acceptability of taste, which is particularly important when the drug is administered in liquid, chewable, or effervescent dosage forms. For example, the prerequisite for oral drugs to produce a taste response must first be dissolved in the mouth or taken in solution. Therefore, one of the ways to reduce the bitterness of orally administered drugs is to make them into poorly soluble salts and to make their saturated concentration below the threshold for producing taste sensation.

4,Into salt, can extend the patent protection of the drug or circumvent its patent protection

In the R&D process of new drugs, once an active compound is discovered, it is generally applied for a patent on its chemical structure to ensure the novelty of the patent. After the drug is marketed, the developer will further develop its derivatives, such as making salts or changing the crystal form and dosage form, and file subsequent patent applications to obtain the longest possible patent protection period. Nowadays, most new drugs marketed internationally use this type of patent protection.

In addition, drug salting can reduce adverse effects. In developing salt-forming drugs, the key is to select the acid or base with which the drug is salted. The selection of the acid or base should consider its pKa value and safety, as well as the route of administration and dosage form after salting. In conclusion, drug-forming studies and drug-forming evaluations can be conducted to determine the drug-forming properties of drugs better and improve the efficiency of new drug development.

[1] Improvement of solubility and stability of phenazopyridine by drug eutectic and salt [J]

Random thoughts 1/n 💭

Tomorrow is my asynchronous class in Medicinal Organic Chemistry, I'm going to finish the remaining activities there and at the same time my assignment in Pharmacy Informatics to be submitted at noon. However, I'm craving coffee again after drinking it a few moments ago which makes me want to go to cafe tomorrow, but I don't have money to buy coffee XD. I'll make sure to finish the other tasks to eliminate workload.

Middle Term Diaries 2/n 💊🏫

house at evening

07 July 2024

I'm currently doing my assignment in Pharmacy Informatics on Patient Drug Database while reading my lessons for the upcoming quiz on Thursday. I am thankful for my batchmate, who is also my instructor, in the said subject, for teaching us the lessons that might help us in doing our research as we will take it after passing this subject. Thank you for the rating that you have computed, I really work hard to earn so much for that rating. I will not be too complacent because I still have so many things to learn from you. Thank you so much batchmate for everything! I am sorry if sometimes I come to class late, I was going through something. I will do my best not to come to the class late.

So, who is Director Yu to Kang Ji-yun?

LOVE SCOUT (2024)

Laboratoire 9/n 🥼

Laboratory

4,9,13 May 2024

As our final output in Quality Control 2, we were to analyze our chosen drug product which is Amoxicillin 500 mg, both generic and leading brand. We did several quality control tests such as Disintegration<701>, Dissolution<711>, Uniformity of Dosage Units<905>, Capsule Diameter and Width, and UV VIS Spectroscopy based on USP/NF. After conducting those QC tests, we prepared a portfolio of the analysis of Amoxicillin 500 mg capsules in which the contents are Finished Product Specifications, Testing Methods, Certificate of Analysis, Data and Result, Computations, and Documentations of the Experiment based on the PIC/S Guidelines Chapter 4. I enjoyed doing those experiments and creating documents for the Quality Control of drugs. I wish I could do these again in my Internship in Manufacturing Pharmacy in th next years. 🥼💊🧪🧫

📸 Tino, Nicko, Czarina

Laboratoire 3/n 🥼

Laboratory

11,19 October 2023

In our Midterm, we had an experiment on different semisolid dosage forms such as creams, ointments, cold creams, and suppositories. So sad because we weren't able to do the others due to lack of reagents. Overall, it was an amazing day for us to prepare such kind of dosage forms. 🥼🧪 📸 Debbie, Adrian, Czarina

BOTICA Diaries 8/n 💊

Rosales, Pangasinan

13 December 2022

One day after the 1st Pailaw that I'd witnessed. The entire grounds of the Presidencia sparkles as they were covered with Christmas lights. 📸🌲🎄

Reise mit mir 1/n🧳

Random places

Random dates

Travelling to different places gives me a sense of comfort and easiness. 🚌

Random thoughts 5/n 💭

I had a wild and fun conversation with my classmate all this time, all about something green and open-minded XD

“Letters Never Sent”

In flickering light of an oil lamp’s glow,

A boy bends low with ink to sow

The trembling truth he’s never said—

A name, a thought, a heart he bled.

“Dear Lillian,” begins the page,

Penned with hands not yet of age.

His breath held tight, his pulse a thread,

Words unsent, but fully meant.

By the mailbox in the rain,

He stands alone with hope and strain.

Will it reach? Will she reply?

Or will it fade before goodbye?

But footsteps break the quiet night,

She stands beneath the softened light.

She sees the note, she meets his eyes—

No thunder, only small surprise.

She reads, she smiles—no words are said,

But silence glows where fear had bled.

He sees his world within her glance,

And knows he’s had his one true chance.

The years unfold like folded notes,

Soft creases pressed through all he wrote.

They meet again, and once again,

Beside the box where love began.

A letter passed through wrinkled hands,

A bench, a smile, the same old stand.

He reads alone, though not unblessed—

For some replies live in the chest.

Now rain falls soft on rusted blue,

Where children stop and read it too.

And etched in brass beneath the light:

“May all love letters find their flight.”