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Long-Acting Poly(DL:Lactic Acid-Castor Oil) 3:7-Bupivacaine Formulation: Effect of Hydrophobic Additives

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ABSTRACT

Purpose

To reduce formulation viscosity of bupivacaine/poly(DL lactic acid co castor oil) 3:7 without increasing bupivacaine release rates.

Methods

Poly(DL lactic acid) 3:7 was synthesized and bupivacaine formulation prepared by mixing with additives ricinoleic acid or castor oil. In vitro release measurements identified optimum formulation. Anesthetized ICR mice were injected around left sciatic nerve using nerve stimulator with 0.1 mL of formulation. Animals received 10% bupivacaine-polymer formulation with 10% castor oil (p(DLLA:CO)3:7–10% bupi-10% CO) or 15% bupivacaine-polymer with 10% castor oil (p(DLLA:CO)3:7–15% bupi-10% CO). Sensory and motor block were measured.

Results

Viscosity of 10% and 15% bupivacaine-p(DLLA:CO)3:7 formulations was reduced using hydrophobic additives; however, castor oil reduced bupivacaine release rates and eliminated burst effect. Less than 10% of the incorporated bupivacaine was released during 6 h, and less than 25% released in 24 h in vitro. In vivo formulation injection resulted in a 24 h motor block and a sensory block lasting at least 72 h.

Conclusions

Incorporation of hydrophobic low-viscosity additive reduced viscosity in addition to burst release effects. Bupivacaine-polymer formulation with castor oil additive demonstrated prolonged sensory analgesia in vivo, with reduced duration of motor block.

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ACKNOWLEDGMENTS & DISCLOSURES

This research was supported in part by grant no. 5868 from the Chief Scientist Office of the Ministry of Health, Israel, by the Legacy Heritage Science Initiative Program of the Israel Science Foundation (1637/10) and a physician research grant from the Hadassah Hebrew University Medical Center

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Authors and Affiliations

  1. Department of Medicinal Chemistry and Natural Products School of Pharmacy–Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, POB 12000, Israel

    Abraham J. Domb

  2. Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, POB 12000, Israel

    Ludmila Golovanevski & Carolyn F. Weiniger

  3. Center for Drug Delivery and Nanomedicine Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Durham Research Center, 985830, Omaha, Nebraska, 68198–5830, USA

    Marina Sokolsky-Papkov

Authors
  1. Marina Sokolsky-Papkov
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  2. Ludmila Golovanevski
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  3. Abraham J. Domb
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  4. Carolyn F. Weiniger
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Correspondence to Carolyn F. Weiniger.

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Sokolsky-Papkov, M., Golovanevski, L., Domb, A.J. et al. Long-Acting Poly(DL:Lactic Acid-Castor Oil) 3:7-Bupivacaine Formulation: Effect of Hydrophobic Additives. Pharm Res 28, 3265–3273 (2011). https://doi.org/10.1007/s11095-011-0497-3

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  • DOI: https://doi.org/10.1007/s11095-011-0497-3

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