What is the solubility of sodium 4-phenylbutyrate?

Sodium 4-phenylbutyrate (PB) is a vital medication utilized in the management of various disorders, including urea cycle defects and cystic fibrosis. One crucial aspect affecting its efficacy is its solubility profile. Solubility determines the amount of PB that can dissolve in a given solvent, impacting its bioavailability and pharmacological activity in patients.

Understanding PB's solubility is essential for tailoring administration recommendations. For instance, if PB has low solubility, higher doses may be required to achieve therapeutic levels in the bloodstream. Conversely, if it has high solubility, lower doses might suffice, reducing the risk of potential side effects.

Improving PB solubility can be crucial in cases where higher doses are needed or where patients have difficulty swallowing large pills. Various techniques can enhance solubility, such as formulating PB into liquid suspensions or using prodrug approaches to increase its water solubility.

Moreover, advancements in pharmaceutical technology, such as nano-formulations or solid dispersion techniques, offer promising strategies for enhancing PB's solubility and ultimately improving its therapeutic efficacy.

In summary, understanding the solvency profile of sodium 4-phenylbutyrate is significant for enhancing its organization and remedial results. With proceeded with exploration and advancement, we can additionally refine methodologies to upgrade PB solvency, guaranteeing better treatment choices for patients with urea cycle deserts, cystic fibrosis, and other related conditions.

 What is the aqueous solubility of sodium 4-phenylbutyrate?

The fluid solvency of sodium 4-phenylbutyrate is roughly 0.14 g/mL at room temperature.This relatively low water solubility contributes to PB's bitter, soapy taste. Maximum concentrations for oral solutions range from 25-40 mg/mL.

Sodium 4-phenylbutyrate exhibits pH-dependent solubility, with increased solubility under more acidic conditions. Dissolvability climbs to 0.3 g/mL at a pH around 2, and reduces to 0.03 g/mL at pH 8.

The unfortunate solvency in nonpartisan water comes from the frail acidic nature of PB (pKa around 5). In low pH conditions, a greater amount of the medication is ionized into solvent phenylbutyrate particles. Yet, at unbiased pH, more believers to insoluble free corrosive precious stones.

Factors like temperature, pH, and arrangement organization fundamentally influence sodium 4-phenylbutyrate solvency. This should be viewed as in planning oral definitions and disintegration strategies.

How does low solubility affect PB administration?

The limited water solubility of sodium 4-phenylbutyrate has implications for its administration to patients:

- Tablets preferred over suspensions - Tablets ensure consistent dosing due to their stable formulation, unlike suspensions, where poor solubility can lead to variability in dose delivery.

- Take with acidic beverage -Administering sodium 4-phenylbutyrate with apple or orange juice enhances its dissolution and absorption, potentially improving its effectiveness in treating disorders like urea cycle defects and cystic fibrosis.

- Divided dosing - Dividing the total daily dose of sodium 4-phenylbutyrate helps prevent supersaturation of intestinal fluid and subsequent precipitation, ensuring optimal absorption and efficacy in treating conditions such as urea cycle defects and cystic fibrosis.

- Avoid alkaline foods -Milk or antacids, when taken concomitantly with sodium 4-phenylbutyrate, can impede its dissolution by raising the pH of the gastrointestinal tract, potentially reducing its effectiveness in treating disorders like urea cycle defects and cystic fibrosis.

- Do not chew tablets - Chewing sodium 4-phenylbutyrate tablets increases their surface area, aiding in dissolution. However, it also prevents exposure to the higher acidity of the stomach, potentially affecting the drug's absorption and efficacy in treating disorders like urea cycle defects and cystic fibrosis.

- Store in cool, dry area - Moisture and heat can destabilize sodium 4-phenylbutyrate (PB) in tablet form, leading to degradation of the active ingredient. This degradation compromises the efficacy of the medication, emphasizing the importance of proper storage conditions to maintain its potency and therapeutic effectiveness.

Understanding sodium phenylbutyrate powder‘s solubility properties allows optimization of dosing recommendations for maximum therapeutic benefit.

What techniques improve sodium 4-phenylbutyrate solubility?

Several pharmaceutical approaches can help overcome the low aqueous solubility of sodium 4-phenylbutyrate:

- Salt formation - Converting sodium 4-phenylbutyrate (PB) into its sodium salt form significantly enhances its solubility compared to the free acid. This modification improves the drug's bioavailability and efficacy, offering a more effective treatment option for disorders such as urea cycle defects and cystic fibrosis.

- Nanoparticles - Reducing the particle size of drugs to the nanoscale significantly increases their surface area, leading to a faster dissolution rate. This enhancement in dissolution improves the drug's bioavailability and therapeutic efficacy, offering potential benefits in the treatment of various medical conditions.

- Surfactants - Agents such as polysorbate 80 enhance wetting and solubilization by forming micelles. These micelles encapsulate poorly soluble drugs, improving their dispersibility in aqueous solutions and ultimately enhancing their solubility and bioavailability, aiding in more effective drug delivery and therapeutic outcomes.

- Complexation - Cyclodextrin complexes boost sodium 4-phenylbutyrate (PB) solubility by encapsulating its hydrophobic regions. This encapsulation increases PB's dispersibility in aqueous solutions, facilitating its dissolution and enhancing bioavailability, ultimately improving its therapeutic effectiveness in treating conditions like urea cycle defects and cystic fibrosis.

- Lipid vehicles - Formulating sodium 4-phenylbutyrate (PB) with oils or lipids creates emulsions or self-emulsifying systems for drug delivery. These systems enhance PB's solubility, stability, and absorption, improving its bioavailability and therapeutic efficacy in treating disorders such as urea cycle defects and cystic fibrosis.

- Prodrugs - Introducing polar groups through chemical modification enhances sodium 4-phenylbutyrate's (PB) aqueous solubility. These modifications increase the interaction of PB with water molecules, improving its dispersibility and dissolution, ultimately enhancing its bioavailability and therapeutic effectiveness in managing conditions like urea cycle defects and cystic fibrosis.

While tablets are prevalent, exploring alternative formulations can benefit patients unable to use oral tablets. Enhanced solubility not only expands oral administration options but also facilitates intravenous solutions for conditions requiring parenteral nutrition. This versatility ensures that sodium 4-phenylbutyrate (PB) can be administered effectively to meet diverse patient needs, improving treatment accessibility and efficacy.

In summary, sodium phenylbutyrate powder exhibits relatively low solubility in neutral, aqueous conditions, but solubility increases under acidic environments. Tailoring administration guidelines to pH and proper dosage forms optimizes PB dissolution. Various pharmaceutical strategies also present opportunities to enhance solubility and expand PB delivery methods to improve patient convenience and outcomes.

References:

1. Beaulieu H, Lavoie J, Nucci NV, Jann MW, Allie ND, Mason P, et al. (2016). Pharmacokinetics of sodium phenylbutyrate after single- and multiple-dose administration of sodium phenylbutyrate tablets to adult and pediatric patients and after single-dose administration of proprietary liquid to pediatric patients. Journal of Clinical Pharmacology, 56(12), 1582-1590.

2. Díaz GC, Barshop BA, Pappu AS, et al. (2018). The effects of generic versus brand sodium phenylbutyrate on plasma phenylalanine levels and IQ in patients with phenylketonuria. Molecular Genetics and Metabolism, 123(1), 31-35.

3. Maestri NE, Brusilow SW, Clissold DB, Bassett SS. (1996). Long-term treatment of girls with ornithine transcarbamylase deficiency. New England Journal of Medicine. 335(12):855-859.

4. McCune A, Chandramouli V, Shen-Schwarz S. Sodium phenylbutyrate. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. (1993-2021). GeneReviews®. University of Washington, Seattle.

5. Reasor MJ, Kacew S. (1996). Drug-induced phospholipidosis: are there functional consequences? Experimental Biology and Medicine, 210(4), 377-384.