Chemically, high-temperature hydrogenation of nitrones or sugars yields D-Sorbitol (Sorbitol). Through an enzymatic mechanism, bacteria like Zymomonas mobilis and Candida boidini can also create D-Sorbitol (Sorbitol) [1]. (Sorbitol) starts the plasticizer in the tablet film coating and the capsule's fast disintegrant. D-sorbitol, often known as sorbitol, is used as a medication stabilizer and sugar substitute in oral solutions. Additionally, D-sorbitol (sorbitol) is frequently used to solubilize medications like indomethacin. Sorbitol, also known as D-Sorbitol, is frequently used in lyophilized parenteral protein formulations as an isotonic agent and/or stabilizing excipient. -In certain preparations, sorbitol functions as a humectant [1].

Absorption, Distribution and Excretion
Sorbitol is primarily excreted through the kidneys in urine or metabolized into carbon dioxide and glucose. This study used a modified ion-exchange resin column treatment method to determine the 24-hour urinary excretion of sorbitol (SOR) in two groups of subjects: diabetic patients and non-diabetic patients, and compared it with the SOR level in whole blood. Simultaneously, the urinary SOR concentration in diabetic rats and normal rats was measured using the same method, and its relationship with aldose reductase (AR) activity in whole blood was investigated. After administration of an AR inhibitor (ARI), changes in urinary and whole blood SOR levels in diabetic rats were compared. The results showed that the whole blood SOR level and urinary SOR excretion were significantly higher in diabetic patients than in non-diabetic patients. Similar results were obtained in animal models. In diabetic rats, urinary SOR excretion was approximately five times that of control rats, and whole blood AR activity was also significantly increased. Administration of ARIs inhibited the increase in urinary SOR excretion, whole blood SOR level, and blood AR activity in diabetic states. The effects of diabetic status and the efficacy of ARIs on urinary SOR excretion were more significant than on whole blood SOR levels. These data suggest that measuring urinary SOR excretion and AR activity is simple and convenient, and helpful in assessing diabetic condition. Accelerated activation of the polyol pathway in diabetes is a crucial factor leading to diabetic complications. To elucidate the mechanisms of diabetic nephropathy with renal tubular damage, we measured urinary sorbitol concentration and urinary N-acetyl-D-glucosidase (NAG) excretion in WBN-kob diabetic rats. Results showed that 24-hour urinary sorbitol concentration in diabetic rats increased synchronously with whole blood sorbitol concentration. The increase in 24-hour urinary NAG excretion was consistent with the increase in urinary sorbitol levels in diabetic rats. Administration of the aldose reductase inhibitor epalrestat reduced whole blood and urinary sorbitol concentrations and urinary NAG excretion in diabetic rats, while also inhibiting renal aldose reductase activity. These results indicate that diabetic nephropathy involves renal tubular cell dysfunction, and that epalrestat treatment may at least halt the progression of the disease. This study aimed to determine whether sorbitol concentrations in cerebrospinal fluid (CSF) were elevated in patients with non-medical conditions (patients with mood disorders). Thirty subjects (10 patients with bipolar disorder, 10 patients with unipolar disorder, and 10 age-matched healthy controls) underwent lumbar puncture, and CSF sorbitol concentrations were measured using gas chromatography-mass spectrometry (GC-MS). The mean ± standard deviation of CSF sorbitol concentrations in the three groups were as follows: bipolar disorder group (22.9 ± 4.6 μmol/L) > unipolar disorder group (19.0 ± 2.8 μmol/L) > healthy control group (15.6 ± 1.9 μmol/L). One-way ANOVA showed significant differences among the three groups (P = 0.0002). Post-hoc tests showed significant differences between the bipolar group and the healthy control group, between the bipolar group and the unipolar group, and between the unipolar group and the healthy control group (P < 0.05).
A diabetic rat model was established by intravenous injection of streptozotocin (Str, 35 mg/kg). Blood glucose levels and sorbitol content in the sciatic nerve and lens were measured at 1 day, 2 months, 5 months, and 8 months after the establishment of the diabetic model. Eight months after the establishment of the diabetic model, sorbitol concentrations in serum, heart, diaphragm, small intestine, and kidney were measured. Results: Following Str injection, diabetic rats exhibited hyperglycemia (>1.7 gL⁻¹), increased appetite, polyuria, polydipsia, and weight loss. Sorbitol levels in the lens and sciatic nerve were elevated in both normal and diabetic rats; the increase was more pronounced in diabetic rats. No correlation was found between blood glucose levels and sorbitol levels. Eight months after the establishment of the diabetic model, sorbitol levels in the small intestine and kidney were elevated…
For more complete data on the absorption, distribution, and excretion of D-sorbitol (8 items), please visit the HSDB records page.

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Metabolism/Metabolites
Sorbitol is widely used in various pharmaceutical products and is naturally found in many edible fruits and berries. It is absorbed more slowly from the gastrointestinal tract than sucrose and is metabolized in the liver into fructose and glucose… Diabetic patients tolerate sorbitol better than sucrose and it is widely used in many sugar-free liquid carriers…
70% of orally ingested sorbitol is converted into carbon dioxide and does not appear in the bloodstream as glucose…

Interactions
Objective: Using ranitidine and metoprolol as model drugs, this study investigated the effects of common excipients (such as sugars, like sorbitol and sucrose) on the bioequivalence of drug formulations. Methods: Two single-dose, replicated, crossover studies were first conducted in healthy volunteers (20 participants per group) to compare the effects of 5 g sorbitol and sucrose on the bioequivalence of 150 mg ranitidine or 50 mg metoprolol aqueous solution. Subsequently, a single-dose, non-replicated, crossover study (24 participants) was conducted to determine the threshold effect of sorbitol on the bioequivalence of 150 mg ranitidine solution. Results: Compared with sucrose, sorbitol reduced the Cmax and AUC0-∞ of ranitidine by approximately 50% and 45%, respectively. Similarly, sorbitol reduced the Cmax of metoprolol by 23%, but had no significant effect on AUC0-∞. Significant subject-formulation interactions were observed in the Cmax and AUC0-∞ of ranitidine and the Cmax of metoprolol. Sorbitol reduced the systemic exposure of ranitidine in a dose-dependent manner and affected bioequivalence at doses of 1.25 g or higher. Conclusion: As demonstrated by sorbitol, some commonly used excipients can have unexpected effects on bioavailability/bioequivalence, depending on the pharmacokinetic characteristics of the drug and the type and amount of excipients in the formulation. Further studies are needed to examine other commonly used excipients that may have unexpected effects on bioavailability/bioequivalence.

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Non-human toxicity values
Rat subcutaneous LD50: 29,600 mg/kg
Rat intravenous LD50: 7100 mg/kg
Rat oral LD50: 15,900 mg/kg
Mouse oral LD50: 17,800 mg/kg
Mouse intravenous LD50: 9480 mg/kg

[1]. Use of sorbitol as pharmaceutical excipient in the present day formulations - issues and challenges for drug absorption and bioavailability. Drug Dev Ind Pharm. 2019 Sep;45(9):1421-1429.

Therapeutic Uses
Sorbitol is a polyol with a sweetness approximately half that of sucrose. It occurs naturally and can also be synthesized from glucose. Formerly used as a diuretic, it is still used as a laxative and in irrigation solutions for certain surgical procedures. It is also used in numerous manufacturing processes, as a pharmaceutical adjuvant, and in various research applications. This report aims to describe a cost-effective strategy for managing constipation in nursing home patients with dementia. …A prospective observational quality improvement study investigated 41 residents with chronic constipation who were receiving osmotic laxatives. Sorbitol was used instead of lactulose. …The frequency and dosage of laxative use over 4 weeks required to maintain normal bowel function were measured. Results: There was no difference in efficacy between lactulose and sorbitol. Other laxatives are rarely used…
Osmotic diuretics, administered intravenously as a 50% (weight/volume) solution, are used to reduce edema, lower cerebrospinal fluid pressure, or reduce intraocular pressure in patients with glaucoma… Dosage: 50 to 100 ml of 50% solution; orally, 30-50 g as a laxative. /Previous Uses/
For more complete data on the therapeutic uses of D-sorbitol (8 in total), please visit the HSDB record page.

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Drug Warnings
Contraindicated for injection. /Sorbitol Solution USP/
Laxatives alone are ineffective in treating poisoning and are not recommended as a method of bowel cleansing. Experimental data on the combined use of laxatives and activated charcoal are conflicting. No clinical studies have been published exploring whether laxatives (with or without activated charcoal) reduce drug bioavailability or improve prognosis in poisoning patients. Based on available data, routine use of laxatives in combination with activated charcoal is not recommended. If laxatives are used, they should be limited to a single dose to minimize adverse reactions.
Side effects are rare after rectal administration of glycerin or sorbitol…rectal discomfort, irritation, burning or cramping, spasmodic pain, and tenesmus (difficulty in defecation). Rectal mucosal congestion with minor bleeding and mucus secretion…occurs less frequently after rectal administration of sorbitol.
Diarrhea is common when sorbitol is used as an adjunct to sodium polystyrene sulfonate therapy.
For more complete data on drug warnings for D-sorbitol (15 in total), please visit the HSDB record page.

C6H14O6

182.17

182.079

50-70-4

D-Sorbitol-d8;287962-59-8;D-Sorbitol-13C;287100-73-6;L-Sorbitol;6706-59-8;D-Sorbitol-d4;2714472-87-2;D-Sorbitol-18O-1;D-Sorbitol-13C6;121067-66-1;D-Sorbitol-13C-1;D-Sorbitol-13C-2;D-Sorbitol-d2;1931877-15-4;D-Sorbitol-d-2;1931877-16-5;D-Sorbitol-d2-1;2714432-33-2;D-Sorbitol-d2-2;1931877-14-3

5780

White to off-white solid powder

1.6±0.1 g/cm3

494.9±0.0 °C at 760 mmHg

98-100 °C (lit.)

>100°C

<0.1 mm Hg ( 25 °C)

1.597

-4.67

6

6

5

12

105

4

C([C@H]([C@H]([C@@H]([C@H](CO)O)O)O)O)O

FBPFZTCFMRRESA-JGWLITMVSA-N

InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4+,5-,6-/m1/s1

(2R,3R,4R,5S)-hexane-1,2,3,4,5,6-hexol

Glucitol; D-Sorbitol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~548.94 mM)
DMSO : ~100 mg/mL (~548.94 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (13.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (13.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 110 mg/mL (603.83 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)